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Your search keyword '"MESH : Fibroblasts"' showing total 14 results
Start Over Descriptor "MESH : Fibroblasts" Topic 0303 health sciences
14 results on '"MESH : Fibroblasts"'

1. Functional characterization of the AFF (AF4/FMR2) family of RNA-binding proteins: insights into the molecular pathology of FRAXE intellectual disability

Author

Mireille Melko, Samantha Zongaro, Jozef Gecz, Dominique Douguet, Barbara Bardoni, Céline Verheggen, Mounia Bensaid, Institut de pharmacologie moléculaire et cellulaire ( IPMC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ), Department of Genetic Medicine Women's and Children's, University of Adelaide, Université Côte d'Azur ( UCA ), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)

Subjects
MESH : Cell Line, MESH : Molecular Sequence Data, MESH: Sequence Homology, Amino Acid, Gene Expression, RNA-binding protein, MESH: Amino Acid Sequence, MESH: Gene Order, Exon, 0302 clinical medicine, MESH : Protein Transport, Genes, Reporter, Transcription (biology), Gene Order, Genetics (clinical), Genetics, 0303 health sciences, MESH : Amino Acid Sequence, MESH : Sequence Alignment, RNA-Binding Proteins, General Medicine, MESH : Genes, Reporter, Phenotype, MESH : Sequence Homology, Amino Acid, DNA-Binding Proteins, Protein Transport, MESH : Fragile X Syndrome, 030220 oncology & carcinogenesis, RNA splicing, MESH : RNA Splicing, MESH : DNA-Binding Proteins, Intranuclear Space, MESH: Fragile X Syndrome, MESH: Protein Transport, MESH: Gene Expression, RNA Splicing, Molecular Sequence Data, MESH : RNA-Binding Proteins, MESH: Sequence Alignment, MESH: Intranuclear Space, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Cell Line, 03 medical and health sciences, MESH : Fibroblasts, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : HeLa Cells, Amino Acid Sequence, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, Gene, 030304 developmental biology, MESH: Molecular Sequence Data, MESH: Humans, MESH : Gene Order, Sequence Homology, Amino Acid, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH: Genes, Reporter, MESH : Humans, Alternative splicing, RNA, Fibroblasts, MESH: Cell Line, MESH : Gene Expression, MESH: RNA-Binding Proteins, MESH : Intranuclear Space, MESH: Fibroblasts, Fragile X Syndrome, MESH: HeLa Cells, MESH: RNA Splicing, Sequence Alignment, MESH: DNA-Binding Proteins, HeLa Cells
Abstract

International audience; The AFF (AF4/FMR2) family of genes includes four members: AFF1/AF4, AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31. AFF2/FMR2 is silenced in FRAXE intellectual disability, while the other three members have been reported to form fusion genes as a consequence of chromosome translocations with the myeloid/lymphoid or mixed lineage leukemia (MLL) gene in acute lymphoblastic leukemias (ALLs). All AFF proteins are localized in the nucleus and their role as transcriptional activators with a positive action on RNA elongation was primarily studied. We have recently shown that AFF2/FMR2 localizes to nuclear speckles, subnuclear structures considered as storage/modification sites of pre-mRNA splicing factors, and modulates alternative splicing via the interaction with the G-quadruplex RNA-forming structure. We show here that similarly to AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31 localize to nuclear speckles and are able to bind RNA, having a high apparent affinity for the G-quadruplex structure. Interestingly, AFF3/LAF4 and AFF4/AF5q31, like AFF2/FMR2, modulate, in vivo, the splicing efficiency of a mini-gene containing a G-quadruplex structure in one alternatively spliced exon. Furthermore, we observed that the overexpression of AFF2/3/4 interferes with the organization and/or biogenesis of nuclear speckles. These findings fit well with our observation that enlarged nuclear speckles are present in FRAXE fibroblasts. Furthermore, our findings suggest functional redundancy among the AFF family members in the regulation of splicing and transcription. It is possible that other members of the AFF family compensate for the loss of AFF2/FMR2 activity and as such explain the relatively mild to borderline phenotype observed in FRAXE patients.

Published
2011
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2. The Inflammatory Response in Acyl-CoA Oxidase 1 Deficiency (Pseudoneonatal Adrenoleukodystrophy)

Author

Pierre Andreoletti, Stéphane Mandard, Aurore Vluggens, Gérard Lizard, Sander Kersten, Janardan K. Reddy, H. I. El Hajj, Kévin Ragot, Ronald J.A. Wanders, H. R. Waterham, Mustapha Cherkaoui-Malki, Amsterdam Gastroenterology Endocrinology Metabolism, Laboratory Genetic Metabolic Diseases, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Laboratoire Bio-PeroxIL. Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique ( Bio-PeroxIL ), Université de Bourgogne ( UB ), Departments of Clinical Chemistry and Pediatrics, University of Amsterdam [Amsterdam] ( UvA ) -Academic Medical Centre, Nutrition, Metabolism and Genomics Group, Wageningen University and Research Centre [Wageningen] ( WUR ), Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ) -Universiteit van Amsterdam ( UvA ), Institut National de la Santé et de la Recherche Médicale, the Conseil Régional de Bourgogne, the Ministère de l'Enseignement Supérieur et de la Recherche, and the Centre National de la Recherche Scientifique., Mandard, Stéphane, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Laboratoire Bio-PeroxIL. Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique (Bio-PeroxIL), Université de Bourgogne (UB), University of Amsterdam [Amsterdam] (UvA)-Academic Medical Centre, Wageningen University and Research [Wageningen] (WUR), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), and University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Universiteit van Amsterdam (UvA)

Subjects
MESH: Inflammation, peroxisomal disorders, MESH: Osteopontin, medicine.medical_treatment, MESH : Immunohistochemistry, MESH : Transcriptome, chemokine receptors, Voeding, Metabolisme en Genomica, 0302 clinical medicine, Endocrinology, MESH: Reverse Transcriptase Polymerase Chain Reaction, Acyl-CoA oxidase, multiple-sclerosis lesions, MESH : Osteopontin, MESH : Fatty Acids, Cells, Cultured, Oligonucleotide Array Sequence Analysis, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, Oxidase test, MESH : Gene Expression Regulation, Reverse Transcriptase Polymerase Chain Reaction, Fatty Acids, MESH: Acyl-CoA Oxidase, MESH : Reverse Transcriptase Polymerase Chain Reaction, Peroxisome, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Immunohistochemistry, MESH: Gene Expression Regulation, Metabolism and Genomics, 3. Good health, MESH: Fatty Acids, MESH : Oligonucleotide Array Sequence Analysis, Cytokine, Metabolisme en Genomica, ACOX1, Adrenoleukodystrophy, Nutrition, Metabolism and Genomics, MESH : Acyl-CoA Oxidase, medicine.symptom, Inflammation Mediators, MESH: Cells, Cultured, medicine.medical_specialty, MESH : Interleukin-8, MESH : Interleukin-6, MESH: Inflammation Mediators, Inflammation, Biology, in-vitro, MESH : Interleukin-1, MESH : Inflammation Mediators, 03 medical and health sciences, Voeding, Internal medicine, Peroxisomal disorder, nf-kappa-b, MESH : Cells, Cultured, MESH : Fibroblasts, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, gene, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Nutrition, 030304 developmental biology, VLAG, MESH: Humans, MESH : Inflammation, Interleukin-6, MESH: Transcriptome, Interleukin-8, MESH : Humans, MESH: Interleukin-1, MESH: Immunohistochemistry, Fibroblasts, medicine.disease, MESH: Interleukin-6, MESH: Interleukin-8, Gene Expression Regulation, MESH: Fibroblasts, MESH: Oligonucleotide Array Sequence Analysis, cells, Brief Reports, Osteopontin, microarray analysis, Acyl-CoA Oxidase, Transcriptome, interleukin-1, 030217 neurology & neurosurgery, x-linked adrenoleukodystrophy, Interleukin-1
Abstract

Among several peroxisomal neurodegenerative disorders, the pseudoneonatal adrenoleukodystrophy (P-NALD) is characterized by the acyl-coenzyme A oxidase 1 (ACOX1) deficiency, which leads to the accumulation of very-long-chain fatty acids ( VLCFA) and inflammatory demyelination. However, the components of this inflammatory process in P-NALD remain elusive. In this study, we used transcriptomic profiling and PCR array analyses to explore inflammatory gene expression in patient fibroblasts. Our results show the activation of IL-1 inflammatory pathway accompanied by the increased secretion of two IL-1 target genes, IL-6 and IL-8 cytokines. Human fibroblasts exposed to very-long-chain fatty acids exhibited increased mRNA expression of IL-1 alpha and IL-1 beta cytokines. Furthermore, expression of IL-6 and IL-8 cytokines in patient fibroblasts was down-regulated by MAPK, p38MAPK, and Jun N-terminal kinase inhibitors. Thus, the absence of acyl-coenzyme A oxidase 1 activity in P-NALD fibroblasts triggers an inflammatory process, in which the IL-1 pathway seems to be central. The use of specific kinase inhibitors may permit the modulation of the enhanced inflammatory status. (Endocrinology 153: 2568-2575, 2012)

Published
2012
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3. Induction of GADD34 is necessary for dsRNA-dependent interferon-β production and participates in the control of Chikungunya virus infection

Author

Evelina Gatti, Till Wenger, Nuno Cláudio, Enrico K. Schmidt, Alexandre Dalet, Delphine Judith, Thérèse Couderc, Philippe Pierre, Voahirana Camosseto, Giovanna Clavarino, Marc Lecuit, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Microorganismes et Barrières de l'Hôte (Equipe avenir), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] ( LAPM ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Centre National de la Recherche Scientifique ( CNRS ), Biologie des Infections, Institut Pasteur [Paris]-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Equipe avenir Microorganismes et Barrières de l'Hôte, and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
MESH : Cell Line, MESH: Interferon Type I, MESH: 3T3 Cells, viruses, MESH: Thapsigargin, MESH: Unfolded Protein Response, Mice, eIF-2 Kinase, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Protein Phosphatase 1, MESH : eIF-2 Kinase, Protein biosynthesis, MESH: Animals, Phosphorylation, Biology (General), MESH: Alphavirus Infections, 0303 health sciences, Protein translation, MESH: Protein Phosphatase 1, Messenger RNA, 030302 biochemistry & molecular biology, MESH : Thapsigargin, 3T3 Cells, 3. Good health, MESH : Activating Transcription Factor 4, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Interferon Type I, MESH : Unfolded Protein Response, Thapsigargin, Cytokines, Chikungunya infection, Chikungunya virus, MESH : Poly I-C, Research Article, medicine.drug, MESH : 3T3 Cells, MESH : Interleukin-6, QH301-705.5, MESH : Protein Phosphatase 1, Immunology, Immunoblotting, Biology, MESH : Chikungunya virus, Microbiology, MESH: Poly I-C, Cell Line, MESH: eIF-2 Kinase, 03 medical and health sciences, MESH : Interferon-beta, MESH : Interferon Type I, MESH: RNA, Double-Stranded, Virology, MESH : Mice, MESH : Fibroblasts, Genetics, medicine, MESH: Activating Transcription Factor 4, Animals, Protein kinase A, Molecular Biology, MESH: Mice, MESH : Alphavirus Infections, RNA, Double-Stranded, 030304 developmental biology, EIF-2 kinase, MESH: Interferon-beta, Alphavirus Infections, Interleukin-6, MESH : RNA, Double-Stranded, Protein phosphatase 1, MESH: Chikungunya virus, Interferon-beta, Fibroblasts, RC581-607, Activating Transcription Factor 4, Molecular biology, Protein kinase R, MESH: Interleukin-6, MESH: Cell Line, Poly I-C, MESH: Fibroblasts, Unfolded Protein Response, Unfolded protein response, biology.protein, Chikungunya Fever, Parasitology, MESH : Animals, Immunologic diseases. Allergy, Protein synthesis, Interferon type I
Abstract

Nucleic acid sensing by cells is a key feature of antiviral responses, which generally result in type-I Interferon production and tissue protection. However, detection of double-stranded RNAs in virus-infected cells promotes two concomitant and apparently conflicting events. The dsRNA-dependent protein kinase (PKR) phosphorylates translation initiation factor 2-alpha (eIF2α) and inhibits protein synthesis, whereas cytosolic DExD/H box RNA helicases induce expression of type I-IFN and other cytokines. We demonstrate that the phosphatase-1 cofactor, growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a), an important component of the unfolded protein response (UPR), is absolutely required for type I-IFN and IL-6 production by mouse embryonic fibroblasts (MEFs) in response to dsRNA. GADD34 expression in MEFs is dependent on PKR activation, linking cytosolic microbial sensing with the ATF4 branch of the UPR. The importance of this link for anti-viral immunity is underlined by the extreme susceptibility of GADD34-deficient fibroblasts and neonate mice to Chikungunya virus infection., Author Summary Nucleic acids detection by multiple molecular sensors results in type-I interferon production, which protects cells and tissues from viral infections. At the intracellular level, the detection of double-stranded RNA by one of these sensors, the dsRNA-dependent protein kinase also leads to the profound inhibition of protein synthesis. We describe here that the inducible phosphatase 1 co-factor Ppp1r15a/GADD34, a well known player in the endoplasmic reticulum unfolded protein response (UPR), is activated during double-stranded RNA detection and is absolutely necessary to allow cytokine production in cells exposed to poly I:C or Chikungunya virus. Our data shows that the cellular response to nucleic acids can reveal unanticipated connections between innate immunity and fundamental stress pathways, such as the ATF4 branch of the UPR.

Published
2012
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4. DCC constrains tumour progression via its dependence receptor activity

Author

Loraine Jarrosson-Wuilleme, Jean-Yves Scoazec, Guillaume Chazot, Marie Castets, Laura Broutier, Yann Molin, Armelle Paquet, Patrick Mehlen, Nicolas Gadot, Laetitia Mazelin, Marie Brevet, Agnès Bernet, Puisieux, Alain, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Anipath, UFR Médecine Lyon-RTH Laennec, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
Deleted in Colorectal Cancer, MESH : Mutant Proteins, MESH : Receptors, Cell Surface, Apoptosis, Dependence receptor, law.invention, MESH : Adenocarcinoma, Mice, MESH: Mutant Proteins, 0302 clinical medicine, law, Netrin, MESH : Intestinal Neoplasms, MESH: Animals, MESH: Gene Silencing, Receptor, Cells, Cultured, Cancer, MESH: Receptors, Cell Surface, 0303 health sciences, MESH: Genes, APC, Multidisciplinary, MESH : Tumor Suppressor Proteins, Genomics, Netrin-1, DCC Receptor, 3. Good health, 030220 oncology & carcinogenesis, Caspases, MESH: HEK293 Cells, Disease Progression, MESH: Disease Progression, MESH : Mutation, MESH: Cells, Cultured, Genes, APC, MESH: Mutation, Context (language use), Receptors, Cell Surface, Biology, Adenocarcinoma, MESH : Nerve Growth Factors, 03 medical and health sciences, MESH : Mice, MESH : Cells, Cultured, MESH : Fibroblasts, MESH : Gene Silencing, Intestinal Neoplasms, Genetics, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene silencing, Animals, Humans, MESH: Tumor Suppressor Proteins, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene Silencing, Nerve Growth Factors, MESH: Intestinal Neoplasms, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH: Humans, MESH: Caspases, MESH: Nerve Growth Factors, Tumor Suppressor Proteins, MESH: Apoptosis, MESH : Humans, fungi, MESH: Adenocarcinoma, MESH : Disease Progression, Fibroblasts, MESH : Disease Models, Animal, MESH : HEK293 Cells, Disease Models, Animal, MESH : Genes, APC, HEK293 Cells, MESH: Fibroblasts, Immunology, Mutation, Cancer research, Suppressor, Mutant Proteins, MESH : Animals, MESH : Caspases, MESH: Disease Models, Animal, MESH : Apoptosis
Abstract

International audience; The role of deleted in colorectal carcinoma (DCC) as a tumour suppressor has been a matter of debate for the past 15 years. DCC gene expression is lost or markedly reduced in the majority of advanced colorectal cancers and, by functioning as a dependence receptor, DCC has been shown to induce apoptosis unless engaged by its ligand, netrin-1 (ref. 2). However, so far no animal model has supported the view that the DCC loss-of-function is causally implicated as predisposing to aggressive cancer development. To investigate the role of DCC-induced apoptosis in the control of tumour progression, here we created a mouse model in which the pro-apoptotic activity of DCC is genetically silenced. Although the loss of DCC-induced apoptosis in this mouse model is not associated with a major disorganization of the intestines, it leads to spontaneous intestinal neoplasia at a relatively low frequency. Loss of DCC-induced apoptosis is also associated with an increase in the number and aggressiveness of intestinal tumours in a predisposing APC mutant context, resulting in the development of highly invasive adenocarcinomas. These results demonstrate that DCC functions as a tumour suppressor via its ability to trigger tumour cell apoptosis.

Published
2012
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5. Biological effects of space radiation on human cells: history, advances and outcomes

Author

Mira Maalouf, Nicolas Foray, Marco Durante, Ciblage thérapeutique en Oncologie ( EA3738 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon, equipe 2, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), M., Maalouf, Durante, Marco, N., Foray, Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH : Microscopy, Fluorescence, Health, Toxicology and Mutagenesis, MESH: Microscopy, Fluorescence, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Astronauts, Cosmic Radiation, Cytogenetics, DNA Damage, Fibroblast, Heavy Ions, MESH : DNA Damage, 0303 health sciences, Radiation, Individual susceptibility, Low dose, MESH: Relative Biological Effectiveness, MESH: Heavy Ions, Adaptive response, radiation effects, Heavy Ions, History, 3. Good health, MESH : Radiation Dosage, Risk analysis (engineering), 030220 oncology & carcinogenesis, MESH: Astronauts, Astronauts, MESH: History, 20th Century, history, MESH : Cosmic Radiation, MESH: History, 21st Century, MESH : Heavy Ions, MESH: Radiation Dosage, MESH: Cosmic Radiation, MESH: Radiobiology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Nanotechnology, MESH: Space Flight, 20th Century, History, Biology, Low dose irradiation, Radiation Dosage, History, 21st Century, Fluorescence, MESH : Cytogenetics, Cytogenetics, 03 medical and health sciences, MESH : Fibroblasts, Humans, MESH : Astronauts, Radiology, Nuclear Medicine and imaging, history, Relative Biological Effectiveness, Space Flight, MESH : Relative Biological Effectiveness, MESH: Cytogenetics, 030304 developmental biology, MESH: DNA Damage, MESH: Humans, MESH : Space Flight, MESH : Humans, 21st Century, Humans, Microscopy, Radiobiology, Fibroblasts, History, 20th Century, Space Flight, Space radiation, methods, Radiation Dosage, Radiobiology, Microscopy, Fluorescence, MESH: Fibroblasts, Repeated doses, MESH : Radiobiology, Dose rate, MESH : History, 21st Century, Cosmic Radiation, Relative Biological Effectiveness, DNA Damage, MESH : History, 20th Century
Abstract

International audience; Exposure to radiation is one of the main concerns for space exploration by humans. By focusing deliberately on the works performed on human cells, we endeavored to review, decade by decade, the technological developments and conceptual advances of space radiation biology. Despite considerable efforts, the cancer and the toxicity risks remain to be quantified: 1) the nature and the frequency of secondary heavy ions need to be better characterized in order to estimate their contribution to the dose and to the final biological response; 2) the diversity of radiation history of each astronaut and the impact of individual susceptibility make very difficult any epidemiological analysis for estimating hazards specifically due to space radiation exposure. 3) Cytogenetic data undoubtedly revealed that space radiation exposure produce significant damage in cells. However, our knowledge of the basic mechanisms specific to low-dose, to repeated doses and to adaptive response is still poor. The application of new radiobiological techniques, like immunofluorescence, and the use of human tissue models different from blood, like skin fibroblasts, may help in clarifying all the above items.

Published
2011

6. A novel mutation of the ACADM gene (c.145C>G) associated with the common c.985A>G mutation on the other ACADM allele causes mild MCAD deficiency: a case report

Author

Daniel Rabier, Silvia Napuri-Gouel, Annie Martin-Ponthieu, Michèle Brivet, Niels Gregersen, Monique Fontaine, Brage S. Andresen, Gilbert Briand, Karine Mention-Mulliez, Dries Dobbelaere, Christine Vianey-Saban, Ronald J.A. Wanders, Joseph Vamecq, Anne-Frédérique Dessein, David S. Millington, Laboratoire d'hormonologie, métabolisme-nutrition et oncologie (HMNO), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Research Unit for Molecular Medicine, Aarhus University [Aarhus]-Institute of Clinical Medicine, Department of Biochemistry and Molecular Biology, University of Southern Denmark (SDU), Service de biochimie métabolique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de neurologie pédiatrique, branche épilepsie, Centre de référence des maladies métaboliques héréditaires, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire d'application de Spectrométrie de Masse (LASM), Université de Lille, Droit et Santé, Department of Paediatrics, Duke University Medical Center, Centre de biologie et pathologie Est, Hospices Civils de Lyon (HCL), Laboratory of Genetic Metabolic Diseases, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), This work was supported by grants from the French Ministère de la Santé (PHRC 2003R/ 1903) and FMO (Fédération des Maladies Orphelines)., Aarhus University [Aarhus] - Institute of Clinical Medicine, UNIVERSITY OF SOUTHERN DENMARK, Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Bicêtre, Hôpital Jeanne de Flandre [Lille] - Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Academic Medical Center [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA) - University of Amsterdam [Amsterdam] (UvA), Faculteit der Geneeskunde, BMC, Ed., Amsterdam Gastroenterology Endocrinology Metabolism, and Laboratory Genetic Metabolic Diseases

Subjects
Male, MESH: Oxidation-Reduction, MESH : Lymphocytes, lcsh:Medicine, MESH : Carnitine, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH : Child, Preschool, Compound heterozygosity, Polymerase Chain Reaction, Acyl-CoA Dehydrogenase, 0302 clinical medicine, Genetics(clinical), MESH : Female, Pharmacology (medical), Lymphocytes, MESH : Acyl-CoA Dehydrogenase, MESH : Polymerase Chain Reaction, MESH : Fatty Acids, Cells, Cultured, Genetics (clinical), Skin, Medicine(all), Genetics, 0303 health sciences, MESH: Carnitine, Fatty Acids, MESH: Genetic Predisposition to Disease, MESH: Acyl-CoA Dehydrogenase, General Medicine, MESH : Adult, Pedigree, MESH: Fatty Acids, 3. Good health, Child, Preschool, Mutation (genetic algorithm), Female, MESH : Mutation, Oxidation-Reduction, ACADM Gene, MESH: Cells, Cultured, medicine.drug, Adult, medicine.medical_specialty, MESH: Mutation, MESH: Pedigree, MESH : Male, Biology, 03 medical and health sciences, MESH : Deficiency Diseases, MESH: Skin, Carnitine, Internal medicine, MESH : Cells, Cultured, MESH : Fibroblasts, MESH : Skin, medicine, Humans, Genetic Predisposition to Disease, ACADM, 030304 developmental biology, MESH : Oxidation-Reduction, [SDV.GEN]Life Sciences [q-bio]/Genetics, Newborn screening, MESH: Humans, Research, lcsh:R, MESH : Humans, MESH: Child, Preschool, Acyl CoA dehydrogenase, MESH: Adult, MESH: Polymerase Chain Reaction, Fibroblasts, MCADD, medicine.disease, MESH: Male, Endocrinology, MESH: Deficiency Diseases, MESH: Fibroblasts, MESH : Pedigree, Mutation, biology.protein, MESH : Genetic Predisposition to Disease, MESH: Lymphocytes, Deficiency Diseases, MESH: Female, 030217 neurology & neurosurgery
Abstract

A female patient, with normal familial history, developed at the age of 30 months an episode of diarrhoea, vomiting and lethargy which resolved spontaneously. At the age of 3 years, the patient re-iterated vomiting, was sub-febrile and hypoglycemic, fell into coma, developed seizures and sequels involving right hemi-body. Urinary excretion of hexanoylglycine and suberylglycine was low during this metabolic decompensation. A study of pre- and post-prandial blood glucose and ketones over a period of 24 hours showed a normal glycaemic cycle but a failure to form ketones after 12 hours fasting, suggesting a mitochondrial β-oxidation defect. Total blood carnitine was lowered with unesterified carnitine being half of the lowest control value. A diagnosis of mild MCAD deficiency (MCADD) was based on rates of 1-14C-octanoate and 9, 10-3H-myristate oxidation and of octanoyl-CoA dehydrogenase being reduced to 25% of control values. Other mitochondrial fatty acid oxidation proteins were functionally normal. De novo acylcarnitine synthesis in whole blood samples incubated with deuterated palmitate was also typical of MCADD. Genetic studies showed that the patient was compound heterozygous with a sequence variation in both of the two ACADM alleles; one had the common c.985A>G mutation and the other had a novel c.145C>G mutation. This is the first report for the ACADM gene c.145C>G mutation: it is located in exon 3 and causes a replacement of glutamine to glutamate at position 24 of the mature protein (Q24E). Associated with heterozygosity for c.985A>G mutation, this mutation is responsible for a mild MCADD phenotype along with a clinical story corroborating the emerging literature view that patients with genotypes representing mild MCADD (high residual enzyme activity and low urinary levels of glycine conjugates), similar to some of the mild MCADDs detected by MS/MS newborn screening, may be at risk for disease presentation.

Published
2010
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7. Fibroblastic reticular cells guide T lymphocyte entry into and migration within the splenic T cell zone

Author

Marc Bajénoff, Ronald N. Germain, Nicolas Glaichenhaus, Lymphocyte Biology Section ( NIAID ), National Institutes of Health, Immunologie des Maladies Infectieuses Allergiques et Autoimmunes, Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Lymphocyte Biology Section (NIAID), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Pathology, MESH: Spleen, MESH: Mice, Mutant Strains, Lymphocyte, MESH: Chemotaxis, Leukocyte, MESH : Arterioles, MESH: T-Lymphocyte Subsets, MESH : Radiation Chimera, 0302 clinical medicine, Reticular cell, Immunology and Allergy, Cytotoxic T cell, MESH: Microscopy, Confocal, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH : Chemokine CCL21, 0303 health sciences, MESH : Adoptive Transfer, MESH : Chemotaxis, Leukocyte, Marginal zone, Cell biology, medicine.anatomical_structure, [SDV.IMM]Life Sciences [q-bio]/Immunology, Lymph, MESH: B-Lymphocyte Subsets, MESH : Spleen, medicine.medical_specialty, MESH: Radiation Chimera, T cell, Immunology, MESH : Mice, Inbred C57BL, Biology, 03 medical and health sciences, MESH: Arterioles, MESH: Mice, Inbred C57BL, MESH : Fibroblasts, MESH : Mice, medicine, MESH : Microscopy, Confocal, MESH: Mice, 030304 developmental biology, MESH: Chemokine CCL21, T lymphocyte, MESH : T-Lymphocyte Subsets, MESH : Mice, Mutant Strains, MESH: Adoptive Transfer, MESH: Fibroblasts, MESH : Stromal Cells, MESH : Animals, MESH: Stromal Cells, Periarteriolar lymphoid sheaths, 030215 immunology, MESH : B-Lymphocyte Subsets
Abstract

Although a great deal is known about T cell entry into lymph nodes, much less is understood about how T lymphocytes access the splenic white pulp (WP). We show in this study that, as recently described for lymph nodes, fibroblastic reticular cells (FRCs) form a network in the T cell zone (periarteriolar lymphoid sheath, PALS) of the WP on which T lymphocytes migrate. This network connects the PALS to the marginal zone (MZ), which is the initial site of lymphocyte entry from the blood. T cells do not enter the WP at random locations but instead traffic to that site using the FRC-rich MZ bridging channels (MZBCs). These data reveal that FRCs form a substrate for T cells in the spleen, guiding these lymphocytes from their site of entry in the MZ into the PALS, within which they continue to move on the same network.

Published
2008

8. Human bone marrow-derived cells: an attractive source to populate dermal substitutes

Author

Philippe Humbert, Myriam Yousfi, Florence Fioretti, Alexis Desmoulière, Corinne Lebreton-Decoster, Gaston Godeau, Farida Gueniche, Bernard Coulomb, Karim Senni, Réparation et remodelage oro-fasciaux, Université Paris Descartes - Paris 5 (UPD5), Interactions de l'épithelium intestinal avec le système immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Université de Limoges (UNILIM), Homéostasie Cellulaire et Pathologies (HCP), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Réparation artérielle (EA 4060), Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Université de Limoges ( UNILIM ), Homéostasie Cellulaire et Pathologies ( HCP ), Université de Limoges ( UNILIM ) -CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ), Réparation artérielle ( EA 4060 ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Saas, Philippe, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
MESH : Wound Healing, Vimentin, Matrix metalloproteinase, Matrix (biology), 030207 dermatology & venereal diseases, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, MESH: Animals, Cells, Cultured, 0303 health sciences, MESH: Middle Aged, biology, integumentary system, Chemistry, MESH : Rats, MESH: Bone Marrow Cells, Anatomy, Dermis, Middle Aged, MESH : Adult, Cell biology, MESH : Skin, Artificial, medicine.anatomical_structure, MESH: Skin, Artificial, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Cells, Cultured, Adult, Cell type, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Rats, Bone Marrow Cells, Dermatology, MESH : Rats, Wistar, Dermal fibroblast, 03 medical and health sciences, MESH : Cells, Cultured, MESH : Fibroblasts, medicine, Animals, Humans, MESH : Middle Aged, Rats, Wistar, 030304 developmental biology, Skin, Artificial, Wound Healing, MESH: Humans, MESH : Humans, MESH : Dermis, MESH: Adult, MESH: Rats, Wistar, Fibroblasts, MESH: Dermis, Rats, MESH: Wound Healing, MESH: Fibroblasts, biology.protein, Surgery, Desmin, MESH : Animals, Wound healing, MESH: Female, MESH : Bone Marrow Cells
Abstract

ACL-92; MMNP; International audience; We have previously shown the importance of dermal fibroblasts within skin substitutes for promoting the emergence of a functional neodermis after grafting in humans. However, the use of fibroblasts from sources other than the dermis needs to be evaluated for patients with extensive skin loss. Here we examined the capacity of human bone marrow-derived cells (BMDCs), selected for their ability to adhere to plastic culture dishes, to behave like human dermal fibroblasts when incorporated within a 3D in vitro reconstructed tissue that promotes dermal fibroblast differentiation. Like dermal fibroblasts, BMDCs contracted a collagen matrix and were growth regulated by the matrix environment. They had the same shape and their nuclei had the same form factor as dermal fibroblasts. In addition, both cell types expressed desmin and vimentin but not alpha-smooth muscle actin. BMDCs deposited collagen types I and III, and fibrillin-1 with similar efficiency to dermal fibroblasts. In addition, BMDCs have the potential to regulate this deposition, as they produced metalloproteinases (MMP1, MMP2, and MMP9) and metalloproteinase inhibitors (TIMP1) very similarly to dermal fibroblasts. BMDCs can thus be induced to express functions resembling those of dermal fibroblasts, including those involved in the wound healing process.

Published
2008
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9. TLR3 deficiency in patients with herpes simplex encephalitis

Author

Vanessa Sancho-Shimizu, Armanda Casrouge, Pedro Romero, Flore Rozenberg, Capucine Picard, Anne Puel, Lluis Quintana-Murci, Asma Smahi, Bénédicte Héron, Frederic Geissmann, Lazaro Lorenzo, Joshua N. Leonard, Jean-Laurent Casanova, Matthias Titeux, Louis Vallée, Luis B. Barreiro, Eric Vivier, Céline Cognet, Horst von Bernuth, Alain Hovnanian, Gaelle Elain, Marc Tardieu, David J. Segal, Shen-Ying Zhang, Emmanuelle Jouanguy, Claire Hamilton, Cheng-Lung Ku, Pierre Lebon, Ariane Chapgier, Laurent Abel, Sophie Ugolini, Sabine Plancoulaine, Xin Xin Zhang, Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service de Chirurgie, Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), and Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )

Subjects
Keratinocytes, MESH : Cell Line, viruses, MESH : Toll-Like Receptor 3, MESH : Immunity, Natural, Herpesvirus 1, Human, CD8-Positive T-Lymphocytes, MESH : Child, Preschool, medicine.disease_cause, 0302 clinical medicine, MESH : Interferons, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Interferons, MESH : Female, Genes, Dominant, MESH: Heterozygote, 0303 health sciences, Toll-like receptor, Multidisciplinary, MESH: Dendritic Cells, MESH : Keratinocytes, MESH: Encephalitis, Herpes Simplex, virus diseases, hemic and immune systems, MESH : Infant, MESH : Genes, Dominant, MESH: Toll-Like Receptor 3, MESH : CD8-Positive T-Lymphocytes, MESH: CD8-Positive T-Lymphocytes, MESH: Infant, MESH: Keratinocytes, 3. Good health, Killer Cells, Natural, MESH: Leukocytes, Mononuclear, MESH: Herpesvirus 1, Human, Child, Preschool, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Killer Cells, Natural, MESH : Mutation, Encephalitis, MESH : Poly I-C, MESH: Killer Cells, Natural, UNC93B1, Heterozygote, MESH : Heterozygote, MESH: Mutation, chemical and pharmacologic phenomena, Biology, MESH: Poly I-C, Virus, Herpesviridae, Cell Line, 03 medical and health sciences, Immunity, MESH : Fibroblasts, medicine, Humans, Alleles, 030304 developmental biology, MESH: Immunity, Natural, Innate immune system, MESH: Humans, MESH: Alleles, MESH: Child, Preschool, MESH : Humans, Infant, Dendritic Cells, Fibroblasts, medicine.disease, Virology, MESH : Herpesvirus 1, Human, Immunity, Innate, MESH : Encephalitis, Herpes Simplex, Toll-Like Receptor 3, MESH: Cell Line, MESH : Leukocytes, Mononuclear, Herpes simplex virus, Poly I-C, MESH: Fibroblasts, MESH : Dendritic Cells, Immunology, Mutation, Leukocytes, Mononuclear, Encephalitis, Herpes Simplex, Interferons, MESH: Genes, Dominant, MESH : Alleles, MESH: Female, 030215 immunology
Abstract

International audience; Some Toll and Toll-like receptors (TLRs) provide immunity to experimental infections in animal models, but their contribution to host defense in natural ecosystems is unknown. We report a dominant-negative TLR3 allele in otherwise healthy children with herpes simplex virus 1 (HSV-1) encephalitis. TLR3 is expressed in the central nervous system (CNS), where it is required to control HSV-1, which spreads from the epithelium to the CNS via cranial nerves. TLR3 is also expressed in epithelial and dendritic cells, which apparently use TLR3-independent pathways to prevent further dissemination of HSV-1 and to provide resistance to other pathogens in TLR3-deficient patients. Human TLR3 appears to be redundant in host defense to most microbes but is vital for natural immunity to HSV-1 in the CNS, which suggests that neurotropic viruses have contributed to the evolutionary maintenance of TLR3.

Published
2007
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10. Bsr, a nuclear-retained RNA with monoallelic expression

Author

Jérôme Cavaillé, Maud Marques, Eugenia Basyuk, Edouard Bertrand, Virginie Marty, Hélène Royo, Laboratoire de biologie moléculaire eucaryote du CNRS ( LBME ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génomique Fonctionnelle ( IGF ), Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Biologie du Développement de Marseille ( IBDM ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherches sur la Cognition Animale [Toulouse] ( CRCA ), Institut de minéralogie et de physique des milieux condensés ( IMPMC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IPG PARIS-Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Departament Geodinàmica i Geofísica, Facultat de Geologia, Laboratoire de Physique Statistique de l'ENS ( LPS ), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris ( FRDPENS ), Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Colloïdes et Matériaux Divisés ( LCMD ), ESPCI ParisTech-Centre National de la Recherche Scientifique ( CNRS ), Liquides Ioniques et Interfaces Chargées ( LI2C ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -ESPCI ParisTech-Centre National de la Recherche Scientifique ( CNRS ), Ecole Nationale de la Santé Publique ( ENSP ), École des Hautes Études en Santé Publique [EHESP] ( EHESP ), Centre de recherches Paul Pascal ( CRPP ), Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de biologie moléculaire eucaryote (LBME), Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Département de biologie [Sherbrooke] (UdeS), Faculté des sciences [Sherbrooke] (UdeS), Université de Sherbrooke (UdeS)-Université de Sherbrooke (UdeS), Laboratoire de Physique Statistique de l'ENS (LPS), Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Colloïdes et Matériaux Divisés (LCMD), Centre National de la Recherche Scientifique (CNRS)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Liquides Ioniques et Interfaces Chargées (LI2C), Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Ecole Nationale de la Santé Publique (ENSP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre de recherches Paul Pascal (CRPP), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur la Cognition Animale - UMR5169 (CRCA), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris)

Subjects
MESH: Hydroxamic Acids, RNA, Untranslated, MESH : RNA, Messenger, MESH: Introns, RNA Stability, Hydroxamic Acids, RNA Transport, MESH: RNA, Untranslated, 0302 clinical medicine, MESH: RNA Transport, Transcription (biology), Gene cluster, MESH : RNA, MESH: Animals, MESH : Cell Nucleus Structures, MESH : Female, MESH : RNA Transport, Genetics, 0303 health sciences, MESH : Cell Nucleus, MESH : Rats, MESH: RNA Stability, Articles, MESH : RNA Stability, Non-coding RNA, medicine.anatomical_structure, RNA splicing, Female, MESH : RNA Splicing, MESH: Cell Nucleus, MESH : RNA, Untranslated, MESH: Rats, RNA Splicing, MESH: Cytoplasmic Granules, Biology, Cytoplasmic Granules, MESH : Rats, Wistar, MESH : Introns, 03 medical and health sciences, MESH: RNA, MESH : Fibroblasts, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Cell Nucleus Structures, RNA, Messenger, Rats, Wistar, Molecular Biology, Gene, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Alleles, MESH: RNA, Messenger, 030304 developmental biology, Cell Nucleus, MESH : Hydroxamic Acids, MESH: Alleles, MESH : Cytoplasmic Granules, Intron, RNA, MESH: Rats, Wistar, Cell Biology, Fibroblasts, Cell Nucleus Structures, Introns, Rats, Cell nucleus, MESH: Fibroblasts, MESH : Animals, MESH: RNA Splicing, MESH : Alleles, MESH: Female, 030217 neurology & neurosurgery
Abstract

The imprinted Dlk1-Gtl2 and Prader-Willi syndrome (PWS) regions are characterized by a complex noncoding transcription unit spanning arrays of tandemly repeated C/D RNA genes. These noncoding RNAs (ncRNAs) are thought to play an essential but still poorly understood role. To better understand the intracellular fate of these large ncRNAs, fluorescence in situ hybridization was carried out at the rat Dlk1-Gtl2 domain. This locus contains a ∼100-kb-long gene cluster comprising 86 homologous RBII-36 C/D RNA gene copies, all of them intron-encoded within the ncRNA gene Bsr. Here, we demonstrate that the Bsr gene is monoallelically expressed in primary rat embryonic fibroblasts as well as in hypothalamic neurons and yields a large amount of unspliced and spliced RNAs at the transcription site, mostly as elongated RNA signals. Surprisingly, spliced Bsr RNAs released from the transcription site mainly concentrate as numerous, stable nuclear foci that do not colocalize with any known subnuclear structures. On drug treatments, a fraction of Bsr RNA relocalizes to the cytoplasm and associates with stress granules (SGs), but not with P-bodies, pointing to a potential link between SGs and the metabolism of ncRNA. Thus, Bsr might represent a novel type of nuclear-retained transcript.

Published
2007
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11. Skin involvement in scleroderma--where histological and clinical scores meet

Author

Raphaël Porcher, Laurence Michel, Patrick Bruneval, Franck Verrecchia, Kiet Phuong Tiev, M. Ertault, O. Verola, Dominique Farge, Alain Mauviel, Nina Roos, J. Laboureau, Bases Moleculaires de l'Homeostasie Cutanee : Inflammation, Reparation et Cancer, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Biostatistique et épidemiologie clinique, Service d'anatomo-pathologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Service greffe de moelle osseuse, Service de médecine interne, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Service de Médecine Interne [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de médecine interne [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de médecine interne [CHU Saint-Antoine], and Verrecchia, Franck

Subjects
Male, Pathology, Systemic disease, MESH: Combined Modality Therapy, MESH : Peripheral Blood Stem Cell Transplantation, Biopsy, MESH : Aged, Smad Proteins, MESH: Peripheral Blood Stem Cell Transplantation, Systemic scleroderma, Severity of Illness Index, Scleroderma, Immunoenzyme Techniques, MESH: Biopsy, 0302 clinical medicine, Fibrosis, Transforming Growth Factor beta, Immunopathology, MESH: Collagen, Pharmacology (medical), MESH: Double-Blind Method, MESH : Female, Phosphorylation, MESH : Immunosuppressive Agents, Cells, Cultured, Skin, MESH: Aged, 0303 health sciences, MESH: Phosph, MESH: Middle Aged, medicine.diagnostic_test, integumentary system, Middle Aged, MESH : Adult, Connective tissue disease, Combined Modality Therapy, 3. Good health, MESH: Fibrosis, MESH : Fibrosis, Female, Collagen, MESH: Immunosuppressive Agents, Reticular Dermis, Immunosuppressive Agents, Signal Transduction, MESH: Cells, Cultured, Adult, medicine.medical_specialty, MESH : Male, Collagen Type I, 03 medical and health sciences, Rheumatology, Double-Blind Method, MESH : Immunoenzyme Techniques, Plasminogen Activator Inhibitor 1, MESH : Cells, Cultured, MESH : Fibroblasts, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, MESH : Double-Blind Method, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Middle Aged, RNA, Messenger, Smad3 Protein, MESH: Immunoenzyme Techniques, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Aged, 030203 arthritis & rheumatology, Peripheral Blood Stem Cell Transplantation, MESH: Humans, business.industry, MESH : Phosph, MESH : Humans, MESH: Adult, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, Fibroblasts, medicine.disease, MESH: Male, MESH: Fibroblasts, MESH : Biopsy, Scleroderma, Diffuse, MESH : Collagen, business, MESH : Combined Modality Therapy, [ SDV.MHEP.DERM ] Life Sciences [q-bio]/Human health and pathology/Dermatology, MESH: Female, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract

International audience; OBJECTIVES: A clinico-pathological study in diffuse systemic sclerosis (SSc) patients was performed to analyse whether the skin histological organization and the pro-fibrotic signals elicited by TGF-beta in fibroblasts vary according to the modified Rodnan skin score (mRSS). METHODS: Twenty-seven SSc patients underwent 45 skin biopsies with simultaneous measure of mRSS before or after treatment by immunosuppressive drugs, with or without autologous peripheral haematopoietic stem cell transplantation (HSCT). RESULTS: Double-blind optic microscopy analysis of the biopsies standard extracellular matrix stains allowed to define three histological subgroups: 6 with grade 1 weak fibrosis, 30 with grade 2 moderate fibrosis and 9 with grade 3 severe fibrosis. A significant (P < 0.0001) was identified between the grades of fibrosis and the mRSS. In skin fibroblast cultures, Smad3 phosphorylation levels, as well as mRNA steady-state levels of two transforming growth factor (TGF)-beta/Smad3 targets, COL1A2 and PAI-1, increased in parallel with the mRSS. When compared with pre-transplant values the degree of fibrosis observed after HSCT in the papillary and in the reticular dermis decreased in parallel with the fall in mRSS (n = 5 consecutive patients with repeated biopsies). CONCLUSIONS: The histological extent of skin fibrosis correlates closely with the mRSS. Both parameters appeared to regress after HSCT. The extent of TGF-beta signalling activation in SSc skin fibroblasts appears to parallel the severity of disease.

Published
2007
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12. Coactivator-associated arginine methyltransferase 1 (CARM1) is a positive regulator of the Cyclin E1 gene

Author

Lucas Fauquier, Carmen Rodríguez, Donghang Cheng, Laurence Vandel, Eric Fabbrizio, Charles Theillet, Selma El Messaoudi, Mark T. Bedford, Paul Chuchana, Claude Sardet, Identité et plasticité tumorale, Université Montpellier 1 ( UM1 ) -CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Génotypes et phénotypes tumoraux, CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Genotypes et Phenotypes Tumoraux, Université Montpellier 1 ( UM1 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de biologie du développement ( CBD ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de biologie du développement (CBD), Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI)

Subjects
Protein-Arginine N-Methyltransferases, MESH : RNA, Messenger, MESH : NIH 3T3 Cells, Cell Culture Techniques, MESH: Protein-Arginine N-Methyltransferase, MESH : RNA, Small Interfering, Histones, Mice, 0302 clinical medicine, Genes, Reporter, MESH: RNA, Small Interfering, MESH : Cell Proliferation, MESH: Animals, RNA, Small Interfering, Luciferases, Promoter Regions, Genetic, MESH : Transcription Factor DP1, Cells, Cultured, MESH: Histones, MESH : Genes, cdc, Regulation of gene expression, Swiss 3T3 Cells, MESH : Trans-Activators, 0303 health sciences, MESH : Protein-Arginine N-Methyltransferase, Multidisciplinary, MESH: Kinetics, MESH : Gene Expression Regulation, Biological Sciences, MESH : Genes, Reporter, MESH: Gene Expression Regulation, MESH : Activin Receptors, Type I, Nucleosomes, MESH: Promoter Regions (Genetics), CCNE1 Gene, MESH: E2F Transcription Factors, 030220 oncology & carcinogenesis, MESH: Transcription Factor DP1, MESH : Kinetics, MESH: Activin Receptors, Type I, Transcription Factor DP1, MESH: Swiss 3T3 Cells, MESH: Cells, Cultured, MESH : Cell Culture Techniques, CARM1, MESH: Trans-Activators, MESH : Swiss 3T3 Cells, MESH : Nucleosomes, Biology, Methylation, MESH: Methylation, 03 medical and health sciences, MESH: Nucleosomes, MESH: Cell Proliferation, MESH : Mice, MESH : Cells, Cultured, MESH : Fibroblasts, Coactivator, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Histones, RNA, Messenger, MESH: Mice, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: RNA, Messenger, MESH : E2F Transcription Factors, 030304 developmental biology, Cell Proliferation, MESH : Luciferases, MESH: Cell Culture Techniques, Reporter gene, Activator (genetics), MESH: Genes, Reporter, Promoter, MESH : Methylation, Fibroblasts, MESH : Promoter Regions (Genetics), Molecular biology, E2F Transcription Factors, Genes, cdc, MESH : MicroRNAs, Cyclin E1, Kinetics, MicroRNAs, MESH: Genes, cdc, Gene Expression Regulation, MESH: Fibroblasts, NIH 3T3 Cells, Trans-Activators, MESH: Luciferases, MESH : Animals, MESH: MicroRNAs, Activin Receptors, Type I, MESH: NIH 3T3 Cells
Abstract

The Cyclin E1 gene ( CCNE1 ) is an ideal model to explore the mechanisms that control the transcription of cell cycle-regulated genes whose expression rises transiently before entry into S phase. E2F-dependent regulation of the CCNE1 promoter was shown to correlate with changes in the level of H3-K9 acetylation/methylation of nucleosomal histones positioned at the transcriptional start site region. Here we show that, upon growth stimulation, the same region is subject to variations of H3-R17 and H3-R26 methylation that correlate with the recruitment of coactivator-associated arginine methyltransferase 1 (CARM1) onto the CCNE1 and DHFR promoters. Accordingly, CARM1-deficient cells lack these modifications and present lowered levels and altered kinetics of CCNE1 and DHFR mRNA expression. Consistently, reporter gene assays demonstrate that CARM1 functions as a transcriptional coactivator for their E2F1/DP1-stimulated expression. CARM1 recruitment at the CCNE1 gene requires activator E2Fs and ACTR, a member of the p160 coactivator family that is frequently overexpressed in human breast cancer. Finally, we show that grade-3 breast tumors present coelevated mRNA levels of ACTR and CARM1 , along with their transcriptional target CCNE1 . All together, our results indicate that CARM1 is an important regulator of the CCNE1 gene.

Published
2006
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13. Involvement of the serotonin 5-HT2B receptor in cardiac hypertrophy linked to sympathetic stimulation: control of interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha cytokine production by ventricular fibroblasts

Author

Jean-Marie Launay, Nelly Etienne, Laurent Monassier, Jacques Callebert, Luc Maroteaux, Fabrice Jaffré, Alexandre Sarre, Canan G. Nebigil, Institut du Fer à Moulin, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Biochimie et de Biologie moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]-Faculté de Pharmacie, Laboratoire de neurobiologie et pharmacologie cardiovasculaire ( LNPCV ), Université de Strasbourg ( UNISTRA ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Faculté de Pharmacie-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de neurobiologie et pharmacologie cardiovasculaire (LNPCV), Université de Strasbourg (UNISTRA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Faculté de Pharmacie, and Maroteaux, Luc

Subjects
Pyridines, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ SDV.MHEP.PSM ] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, MESH : Adrenergic beta-Agonists, MESH: Myocytes, Cardiac, Stimulation, MESH: Adrenergic beta-Agonists, Muscle hypertrophy, Propanolamines, Mice, 0302 clinical medicine, MESH : Receptor, Serotonin, 5-HT2B, MESH : Indoles, Adrenergic beta-2 Receptor Antagonists, Receptor, Serotonin, 5-HT2B, MESH: Animals, MESH : Drug Evaluation, Preclinical, Sympathomimetics, Cells, Cultured, MESH: Indoles, 0303 health sciences, MESH : Gene Expression Regulation, Adrenergic beta-1 Receptor Antagonists, 3. Good health, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Serotonin 5-HT2 Receptor Antagonists, cardiovascular system, Tumor necrosis factor alpha, Cardiology and Cardiovascular Medicine, MESH : Sympathetic Nervous System, MESH: Cells, Cultured, Cardiac function curve, medicine.medical_specialty, MESH : Adrenergic beta-1 Receptor Antagonists, Heart Ventricles, MESH : Myocytes, Cardiac, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH : Serotonin Antagonists, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Physiology (medical), MESH : Fibroblasts, MESH: Propanolamines, Tumor Necrosis Factor-alpha, MESH: Pyridines, Isoproterenol, MESH: Interleukin-1, MESH : Propanolamines, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Fibroblasts, MESH: Interleukin-6, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Endocrinology, MESH: Tumor Necrosis Factor-alpha, MESH : Heart Ventricles, MESH : Adrenergic beta-2 Receptor Antagonists, MESH: Receptors, Adrenergic, beta-1, MESH: Heart Ventricles, MESH: Cardiomegaly, MESH: Receptors, Adrenergic, beta-2, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Indoles, Sympathetic Nervous System, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Drug Evaluation, Preclinical, MESH : Receptors, Adrenergic, beta-2, MESH : Isoproterenol, 030204 cardiovascular system & hematology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Mice, Knockout, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Isoproterenol, MESH: Serotonin Antagonists, MESH: Adrenergic beta-2 Receptor Antagonists, Myocytes, Cardiac, MESH: Sympathetic Nervous System, Mice, Knockout, MESH : Tumor Necrosis Factor-alpha, biology, Imidazoles, Interleukin, Adrenergic beta-Agonists, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH: Gene Expression Regulation, 5-HT2B receptor, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cytokine, MESH: Adrenergic beta-1 Receptor Antagonists, MESH: Serotonin 5-HT2 Receptor Antagonists, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Quinolines, MESH: Drug Evaluation, Preclinical, MESH : Receptors, Adrenergic, beta-1, MESH : Cardiomegaly, Serotonin Antagonists, MESH: Quinolines, MESH: Imidazoles, MESH : Pyridines, MESH : Interleukin-6, MESH : Quinolines, Cardiomegaly, [SDV.GEN.GA] Life Sciences [q-bio]/Genetics/Animal genetics, MESH : Interleukin-1, MESH : Imidazoles, Internal medicine, MESH : Cells, Cultured, MESH : Mice, medicine, Animals, MESH : Sympathomimetics, Interleukin 6, MESH: Mice, 030304 developmental biology, business.industry, Interleukin-6, MESH: Sympathomimetics, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Receptor, Serotonin, 5-HT2B, [ SDV.SP.PHARMA ] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [ SDV.GEN.GA ] Life Sciences [q-bio]/Genetics/Animal genetics, Gene Expression Regulation, MESH: Fibroblasts, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, biology.protein, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH : Mice, Knockout, Receptors, Adrenergic, beta-2, MESH : Animals, Receptors, Adrenergic, beta-1, MESH : Serotonin 5-HT2 Receptor Antagonists, business, Interleukin-1
Abstract

Background— The serotonergic 5-HT 2B receptor regulates cardiomyocyte development and growth. A putative contribution of this receptor to fibroblast-dependent cardiac function has not been identified. Methods and Results— By mimicking sympathetic stimulation with chronic isoproterenol perfusion in vivo, we found that mice developed a cardiac hypertrophy, which was prevented by exposure to the 5-HT 2B receptor antagonists SB206553 or SB215505 or in 5-HT 2B receptor–knockout mice. The isoproterenol-induced hypertrophy was associated with an increase in the plasma levels of interleukin-1β and tumor necrosis factor-α but not interleukin-6. In contrast, the plasma isoproterenol-induced cytokine increase was not observed in either 5-HT 2B receptor–mutant or wild-type mice perfused with isoproterenol+SB206553. We demonstrated that stimulation of wild-type cardiac fibroblasts by isoproterenol markedly increased the production of the interleukin-6, interleukin-1β, and tumor necrosis factor-α cytokines. Strikingly, we found that this isoproterenol-induced cytokine production was abolished by SB206553 or in 5-HT 2B receptor–knockout fibroblasts. Serotonin also stimulated production of the 3 cytokines in wild-type fibroblasts, which was effectively reduced in 5-HT 2B receptor–knockout fibroblasts. Conclusions— Our results demonstrate for the first time that 5-HT 2B receptors are essential for isoproterenol-induced cardiac hypertrophy, which involves the regulation of interleukin-6, interleukin-1β, and tumor necrosis factor-α cytokine production by cardiac fibroblasts.

Published
2004
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14. Interleukin-1beta induces glycosaminoglycan synthesis via the prostaglandin E2 pathway in cultured human cervical fibroblasts

Author

Michelle Breuiller-Fouché, Françoise Ferré, Thomas Schmitz, Dominique Cabrol, Emmanuelle Dallot, Marie-Josèphe Leroy, Breuiller-Fouche, Michelle, La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus (UMR_S 767), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maternité Port-Royal [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomique et épigénétique des pathologies placentaires (Inserm U709), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus ( UMR_S 767 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Génomique et épigénétique des pathologies placentaires ( Inserm U709 ), and Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 )

Subjects
MESH : RNA, Messenger, Transcription, Genetic, medicine.medical_treatment, MESH: Sulfonamides, Cervix Uteri, MESH: Base Sequence, 0302 clinical medicine, Cells, Cultured, Glycosaminoglycans, MESH : Isoenzymes, Sulfonamides, 0303 health sciences, 030219 obstetrics & reproductive medicine, MESH: Dinoprostone, MESH: Cervix Uteri, Receptors, Prostaglandin E, EP3 Subtype, MESH : Biphenyl Compounds, MESH : DNA Primers, MESH: Membrane Proteins, Prostaglandin E, MESH: Cells, Cultured, MESH: DNA Primers, medicine.medical_specialty, MESH : Cyclooxygenase 2, MESH: Prostaglandin-Endoperoxide Synthases, Dinoprostone, Article, 03 medical and health sciences, MESH: Cyclooxygenase Inhibitors, MESH : Fibroblasts, Genetics, Humans, Cyclooxygenase Inhibitors, RNA, Messenger, Molecular Biology, Nitrobenzenes, MESH: Humans, Cyclooxygenase 2 Inhibitors, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Biphenyl Compounds, MESH : Humans, MESH: Interleukin-1, Fibroblasts, Receptors, Prostaglandin E, EP2 Subtype, MESH : Nitrobenzenes, Endocrinology, Reproductive Medicine, MESH : Membrane Proteins, MESH: Female, Developmental Biology, Embryology, MESH: Cyclooxygenase 2 Inhibitors, MESH: Receptors, Prostaglandin E, MESH : Cyclooxygenase 2 Inhibitors, MESH : Female, Prostaglandin E2, Receptor, MESH : Prostaglandin-Endoperoxide Synthases, MESH: Kinetics, Obstetrics and Gynecology, Interleukin, MESH: Glycosaminoglycans, MESH : Cyclooxygenase Inhibitors, Receptor antagonist, Receptors, Prostaglandin E, EP1 Subtype, Isoenzymes, MESH: Isoenzymes, lipids (amino acids, peptides, and proteins), Female, Signal transduction, MESH : Kinetics, MESH: Cyclooxygenase 2, MESH : Receptors, Prostaglandin E, MESH: Biphenyl Compounds, medicine.drug, MESH : Dinoprostone, medicine.drug_class, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH : Interleukin-1, Paracrine signalling, Internal medicine, MESH : Cells, Cultured, medicine, MESH : Glycosaminoglycans, Receptors, Prostaglandin E, Autocrine signalling, MESH : Sulfonamides, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, DNA Primers, 030304 developmental biology, MESH: RNA, Messenger, Base Sequence, MESH: Transcription, Genetic, Membrane Proteins, MESH : Transcription, Genetic, MESH: Nitrobenzenes, Cell Biology, Kinetics, Cyclooxygenase 2, Prostaglandin-Endoperoxide Synthases, MESH: Fibroblasts, MESH : Cervix Uteri, MESH : Base Sequence, Receptors, Prostaglandin E, EP4 Subtype, Interleukin-1
Abstract

International audience; The aim of this study was to identify, in cultured human cervical fibroblasts, the mechanisms by which interleukin (IL)-1beta induces the synthesis of glycosaminoglycans (GAG) and to explore the putative role of prostaglandin E(2) (PGE(2)) in this process. Exposure of the cells for 24 h to IL-1beta induced a significant (P < 0.05) dose-dependent increase in GAG synthesis. IL-1beta (1 ng/ml) induced the expression of cyclooxygenase-2 (COX-2) protein 6 h after treatment, accompanied by a 7.5-fold increase in PGE(2) production. We confirmed that NS398, a selective COX-2 inhibitor, dose-dependently blocked PGE(2) augmentation following IL-1beta treatment. AH23848, the selective EP(4) receptor antagonist, completely abolished IL-1beta-induced GAG synthesis, whereas AH6809, an EP(2) receptor antagonist, had no effect on the stimulatory effects of IL-1beta. Furthermore, we demonstrated that 6 h exposure to IL-1beta induced a notable increase in EP(4) receptor mRNA expression and a decrease in EP(1) receptor mRNA but had no effect on the expression of EP(2) and EP(3) receptor transcripts. In conclusion, these findings indicate that IL-1beta not only induced GAG synthesis by increasing COX-2 protein expression and the subsequent PGE(2) production but also enhanced the responsiveness of cervical fibroblasts to PGE(2) by selectively up-regulating EP(4) receptor mRNA expression. These results suggest that PGE(2) may regulate human cervical ripening in an autocrine/paracrine manner via EP(4) receptors.

Published
2003

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