17 results on '"Isabelle Salwig"'
Search Results
2. Depletion of Numb and Numblike in Murine Lung Epithelial Cells Ameliorates Bleomycin-Induced Lung Fibrosis by Inhibiting the β-Catenin Signaling Pathway
- Author
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Alessandro Ianni, Michael Hofmann, Poonam Kumari, Shahriar Tarighi, Hamza M Al-Tamari, André Görgens, Bernd Giebel, Hendrik Nolte, Marcus Krüger, Isabelle Salwig, Soni Savai Pullamsetti, Andreas Günther, André Schneider, and Thomas Braun
- Subjects
lung ,fibrosis ,epithelium ,NUMB ,β-catenin ,Biology (General) ,QH301-705.5 - Abstract
Idiopathic pulmonary fibrosis (IPF) represents the most aggressive form of pulmonary fibrosis (PF) and is a highly debilitating disorder with a poorly understood etiology. The lung epithelium seems to play a critical role in the initiation and progression of the disease. A repeated injury of lung epithelial cells prompts type II alveolar cells to secrete pro-fibrotic cytokines, which induces differentiation of resident mesenchymal stem cells into myofibroblasts, thus promoting aberrant deposition of extracellular matrix (ECM) and formation of fibrotic lesions. Reactivation of developmental pathways such as the Wnt-β-catenin signaling cascade in lung epithelial cells plays a critical role in this process, but the underlying mechanisms are still enigmatic. Here, we demonstrate that the membrane-associated protein NUMB is required for pathological activation of β-catenin signaling in lung epithelial cells following bleomycin-induced injury. Importantly, depletion of Numb and Numblike reduces accumulation of fibrotic lesions, preserves lung functions, and increases survival rates after bleomycin treatment of mice. Mechanistically, we demonstrate that NUMB interacts with casein kinase 2 (CK2) and relies on CK2 to activate β-catenin signaling. We propose that pharmacological inhibition of NUMB signaling may represent an effective strategy for the development of novel therapeutic approaches against PF.
- Published
- 2021
- Full Text
- View/download PDF
3. Broad AOX expression in a genetically tractable mouse model does not disturb normal physiology
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Marten Szibor, Praveen K. Dhandapani, Eric Dufour, Kira M. Holmström, Yuan Zhuang, Isabelle Salwig, Ilka Wittig, Juliana Heidler, Zemfira Gizatullina, Timur Gainutdinov, German Mouse Clinic Consortium, Helmut Fuchs, Valérie Gailus-Durner, Martin Hrabě de Angelis, Jatin Nandania, Vidya Velagapudi, Astrid Wietelmann, Pierre Rustin, Frank N. Gellerich, Howard T. Jacobs, and Thomas Braun
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Mitochondria ,Mitochondrial disease ,Respiratory chain ,Alternative oxidase ,Medicine ,Pathology ,RB1-214 - Abstract
Plants and many lower organisms, but not mammals, express alternative oxidases (AOXs) that branch the mitochondrial respiratory chain, transferring electrons directly from ubiquinol to oxygen without proton pumping. Thus, they maintain electron flow under conditions when the classical respiratory chain is impaired, limiting excess production of oxygen radicals and supporting redox and metabolic homeostasis. AOX from Ciona intestinalis has been used to study and mitigate mitochondrial impairments in mammalian cell lines, Drosophila disease models and, most recently, in the mouse, where multiple lentivector-AOX transgenes conferred substantial expression in specific tissues. Here, we describe a genetically tractable mouse model in which Ciona AOX has been targeted to the Rosa26 locus for ubiquitous expression. The AOXRosa26 mouse exhibited only subtle phenotypic effects on respiratory complex formation, oxygen consumption or the global metabolome, and showed an essentially normal physiology. AOX conferred robust resistance to inhibitors of the respiratory chain in organello; moreover, animals exposed to a systemically applied LD50 dose of cyanide did not succumb. The AOXRosa26 mouse is a useful tool to investigate respiratory control mechanisms and to decipher mitochondrial disease aetiology in vivo.
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- 2017
- Full Text
- View/download PDF
4. Antigen presentation by lung epithelial cells directs CD4+ TRM cell function and regulates barrier immunity
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Anne Hinds, E.I. Arafa, Anukul T. Shenoy, Thomas Braun, Matthew R. Jones, Carolina Lyon De Ana, Filiz Korkmaz, Aditya Ramanujan, Neelou S. Etesami, Kimberly A. Barker, Hasmeena Kathuria, Joseph P. Mizgerd, Alicia M. Soucy, Anna C. Belkina, Brian R. Tilton, Wesley N. Goltry, I.M.C. Martin, Isabelle Salwig, and Lee J. Quinton
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CD4-Positive T-Lymphocytes ,medicine.medical_treatment ,Science ,Cell ,Antigen presentation ,Antigen-presenting cells ,Fluorescent Antibody Technique ,General Physics and Astronomy ,Real-Time Polymerase Chain Reaction ,Immunological memory ,Article ,General Biochemistry, Genetics and Molecular Biology ,Flow cytometry ,Mice ,Immune system ,Microscopy, Electron, Transmission ,Antigen ,Leukocytes ,medicine ,Animals ,Antigen-presenting cell ,Lung ,CD4-positive T cells ,Antigen Presentation ,Multidisciplinary ,medicine.diagnostic_test ,Chemistry ,Epithelial Cells ,General Chemistry ,Flow Cytometry ,Epithelium ,Cell biology ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Cytokine ,Mucosal immunology - Abstract
Barrier tissues are populated by functionally plastic CD4+ resident memory T (TRM) cells. Whether the barrier epithelium regulates CD4+ TRM cell locations, plasticity and activities remains unclear. Here we report that lung epithelial cells, including distinct surfactant protein C (SPC)lowMHChigh epithelial cells, function as anatomically-segregated and temporally-dynamic antigen presenting cells. In vivo ablation of lung epithelial MHC-II results in altered localization of CD4+ TRM cells. Recurrent encounters with cognate antigen in the absence of epithelial MHC-II leads CD4+ TRM cells to co-express several classically antagonistic lineage-defining transcription factors, changes their cytokine profiles, and results in dysregulated barrier immunity. In addition, lung epithelial MHC-II is needed for surface expression of PD-L1, which engages its ligand PD-1 to constrain lung CD4+ TRM cell phenotypes. Thus, we establish epithelial antigen presentation as a critical regulator of CD4+ TRM cell function and identify epithelial-CD4+ TRM cell immune interactions as core elements of barrier immunity., The maintenance of T resident memory (TRM) cells within pulmonary tissues is incompletely understood. Here the authors show that antigen presentation by lung epithelial cells maintains function and phenotype of pulmonary TRM cells within specific locational niches.
- Published
- 2021
5. Imaging lung regeneration by light sheet microscopy
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Birgit Spitznagel, Thomas Braun, Marion Wiesnet, and Isabelle Salwig
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0301 basic medicine ,Histology ,Light ,Short Communication ,Biology ,Club cells ,Regenerative foci ,Mice ,03 medical and health sciences ,Optical clearing ,0302 clinical medicine ,medicine ,Animals ,Stem cell niches ,Lung regeneration ,Progenitor cell ,Molecular Biology ,Mice, Knockout ,Lung ,Regeneration (biology) ,Lung Injury ,Cell Biology ,Cell biology ,Medical Laboratory Technology ,030104 developmental biology ,medicine.anatomical_structure ,Microscopy, Fluorescence ,Light sheet fluorescence microscopy ,Light sheet microscopy ,Respiratory epithelium ,Stem cell ,mCherry ,Developmental biology ,030217 neurology & neurosurgery - Abstract
Optical clearing combined with deep imaging of large biological specimen allows organ-wide visualization of cells in three dimensions (3D) to explore regenerative processes in a spatial context. Here, we investigate the dynamics of airway regeneration following toxin-mediated epithelial injury in cleared whole lung preparations by light sheet microscopy. We use a recently developed knock-in mouse strain labeling bronchiolar Club cells (Scgb1a1-mCherry) to define an optimal clearing procedure that efficiently preserves genetically encoded fluorophores. Dehydration in pH-adjusted tert-butanol followed by clearing in ethyl cinnamate maintained maximum mCherry fluorescence while preventing unfavorable background fluorescence. We apply this technique to depict the course of bronchiolar epithelial renewal from an acute injury phase to early and late recovery stages. 3D reconstructions of whole lungs demonstrate near-complete loss of secretory Club cells throughout the entire respiratory tract 3 days post naphthalene (dpn). Multiple foci of regenerating Club cells emerge at 7 dpn, predominantly at airway bifurcations and in distal terminal bronchioles—anatomical regions assumed to harbor distinct stem/progenitor cells subsets. At 21 dpn, clusters of newly formed Club cells have largely expanded, although the bronchiolar epithelial lining continues to regenerate. This study identifies regional stem cell niches as starting points for epithelial recovery, underscores the enormous regenerative capacity of the respiratory epithelium and demonstrates the power of whole lung 3D imaging for evaluating the extent of pulmonary damage and subsequent repair processes. Electronic supplementary material The online version of this article (10.1007/s00418-020-01903-8) contains supplementary material, which is available to authorized users.
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- 2020
6. Multilineage murine stem cells generate complex organoids to model distal lung development and disease
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Elie El Agha, Saverio Bellusci, Andreas Hoek, Irina Shalashova, Isabelle Salwig, Werner Seeger, Rory E. Morty, Marie Christin Hessler, István Vadász, Alexander Goesmann, Thomas Braun, Andreas Günther, Susanne Herold, Wolfgang Kummer, Jan Philip Mengel, Torsten Hain, Amit Shrestha, Gianni Carraro, Ana Ivonne Vazquez-Armendariz, Martin Schwemmle, and Monika Heiner
- Subjects
Lung Diseases ,Organogenesis ,Respiratory System ,Biology ,Regenerative Medicine ,lung organoids ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,medicine ,Organoid ,Morphogenesis ,Compartment (development) ,Animals ,Humans ,Regeneration ,News & Views ,RNA, Messenger ,Molecular Biology ,Lung ,Ataxin-1 ,Cells, Cultured ,030304 developmental biology ,0303 health sciences ,Gene knockdown ,General Immunology and Microbiology ,General Neuroscience ,Stem Cells ,Mesenchymal stem cell ,RNA ,Endothelial Cells ,BASC ,Cell Differentiation ,Epithelial Cells ,Mesenchymal Stem Cells ,Articles ,Fibroblasts ,Epithelial Cell Adhesion Molecule ,In vitro ,Cell biology ,Organoids ,Pulmonary Alveoli ,medicine.anatomical_structure ,Stem cell ,BALO ,030217 neurology & neurosurgery - Abstract
Organoids derived from mouse and human stem cells have recently emerged as a powerful tool to study organ development and disease. We here established a three‐dimensional (3D) murine bronchioalveolar lung organoid (BALO) model that allows clonal expansion and self‐organization of FACS‐sorted bronchioalveolar stem cells (BASCs) upon co‐culture with lung‐resident mesenchymal cells. BALOs yield a highly branched 3D structure within 21 days of culture, mimicking the cellular composition of the bronchioalveolar compartment as defined by single‐cell RNA sequencing and fluorescence as well as electron microscopic phenotyping. Additionally, BALOs support engraftment and maintenance of the cellular phenotype of injected tissue‐resident macrophages. We also demonstrate that BALOs recapitulate lung developmental defects after knockdown of a critical regulatory gene, and permit modeling of viral infection. We conclude that the BALO model enables reconstruction of the epithelial–mesenchymal‐myeloid unit of the distal lung, thereby opening numerous new avenues to study lung development, infection, and regenerative processes in vitro., Resource work reports a new in vitro system to model the bronchioalveolar airways.
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- 2019
7. Bronchioalveolar stem cells are a main source for regeneration of distal lung epithelia in vivo
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Stefan Guenther, Ana Ivonne Vazquez-Armendariz, Isabelle Salwig, Susanne Herold, Birgit Spitznagel, Thomas Braun, Keynoosh Khalooghi, and Marten Szibor
- Subjects
0303 health sciences ,Lung ,General Immunology and Microbiology ,General Neuroscience ,Regeneration (biology) ,Cell ,RNA ,respiratory system ,Biology ,General Biochemistry, Genetics and Molecular Biology ,respiratory tract diseases ,Cell biology ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,In vivo ,medicine ,Stem cell ,Molecular Biology ,Gene ,030217 neurology & neurosurgery ,Homeostasis ,030304 developmental biology - Abstract
Bronchioalveolar stem cells (BASCs) are a potential source for lung regeneration, but direct in vivo evidence for a multipotential lineage contribution during homeostasis and disease is critically missing, since specific genetic labeling of BASCs has not been possible. We developed a novel cell tracing approach based on intein‐mediated assembly of newly engineered split‐effectors, allowing selective targeting of dual‐marker expressing BASCs in the mouse lung. RNA sequencing of isolated BASCs demonstrates that BASCs show a distinct transcriptional profile, characterized by co‐expression of bronchiolar and alveolar epithelial genes. We found that BASCs generate the majority of distal lung airway cells after bronchiolar damage but only moderately contribute to cellular turnover under homeostatic conditions. Importantly, DTA‐mediated ablation of BASCs compromised proper regeneration of distal airways. The study defines BASCs as crucial components of the lung repair machinery and provides a paradigmatic example for the detection and manipulation of stem cells that cannot be recognized by a single marker alone.
- Published
- 2019
8. Estimation of absolute number of alveolar epithelial type 2 cells in mouse lungs: a comparison between stereology and flow cytometry
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Isabelle Salwig, Rory E. Morty, Christian Mühlfeld, Martin Szibor, István Vadász, Susanne Herold, Werner Seeger, Ann Atzberger, Jordi Ruiz-Camp, Georgy Dzhuraev, Thomas Braun, José Alberto Rodríguez-Castillo, and Katrin Ahlbrecht
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Male ,Pathology ,medicine.medical_specialty ,Histology ,Cell number ,Stereology ,Cell Count ,02 engineering and technology ,Unbiased Estimation ,Biology ,Pathology and Forensic Medicine ,Flow cytometry ,03 medical and health sciences ,Mice ,Imaging, Three-Dimensional ,medicine ,Animals ,Lung ,030304 developmental biology ,0303 health sciences ,medicine.diagnostic_test ,Absolute number ,021001 nanoscience & nanotechnology ,Cell counting ,Flow Cytometry ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Intracellular staining ,Alveolar Epithelial Cells ,Female ,0210 nano-technology - Abstract
Accurate estimation of the absolute number of a particular cell-type in whole organs is increasingly important in studies on organogenesis, and the remodelling and repair of diseased tissues. The unbiased estimation of the absolute number of cells in an organ is complicated, and design-based stereology remains the method of choice. This has led investigators to explore alternative approaches - such as flow cytometry - as a faster and less labour-intensive replacement for stereology. To address whether flow cytometry might substitute stereology, design-based stereology was compared with microfluorosphere-controlled flow cytometry, for estimation of the absolute number of alveolar epithelial type 2 cells (AEC2) in the lungs of two mouse strains: wild-type C57BL/6J mice and Sftpc-YFP mice. Using design-based stereology, ≈10.7 million and ≈9.0 million AEC2 were estimated in the lungs of wild-type C57BL/6J mice and Sftpc-YFP mice, respectively. Substantially fewer AEC2 were estimated using flow cytometry. In wild-type C57/BL6J mouse lungs, 59% of the AEC2 estimated by design-based stereology were estimated by flow cytometry (≈6.3 million), using intracellular staining for pro-surfactant protein C. Similarly, in Sftpc-YFP mouse lungs, 23% of the AEC2 estimated by design-based stereology were estimated by flow cytometry (≈2.1 million), using yellow fluorescent protein fluorescence. Our data suggest that flow cytometry underestimates AEC2 number, possibly due to impaired recoverability of AEC2 from dissociated lung tissue. These data suggest design-based stereology as the method of choice for the unbiased estimation of the absolute number of cells in an organ. LAY DESCRIPTION: There is much interest in studies on the pathological changes that accompany disease, to be able to count or estimate the number of a particular cell-type in solid tissue, such as an organ. The easiest way to do this is to make liquid suspensions of single cells from solid tissue, and then to count the number of cells of interest, using either a microscope, or automated cell counting (for example, a flow cytometer). Alternatively, solid tissue may be examined microscopically, where the cell-type of interest might also be counted 'by eye' or in an automated manner using software (called planimetry). All of these approaches to counting cells in solid organs come with serious drawbacks, and estimation of the cell number may thus be inaccurate. To overcome this, we have employed a combination of mathematical tools and statistical principles together with microscopy (called 'design-based stereology') that permits the unbiased counting of cells in microscopic fields, which can then be extrapolated to the entire solid tissue volume, to accurately estimate the number of a cell-type of interest in the solid tissue. We have compared this method with the estimation of cell number using a flow cytometer. Our data reveal that flow cytometry appreciably underestimates the total number of cells in solid tissue, where we used the lung as an example of solid tissue, and estimated the number of a unique cell-type in the lung: the alveolar epithelial type 2 cell, to compare stereology with flow cytometry. We believe that flow cytometry underestimates the cell number due to the difficulty of breaking up solid tissue into single cells, and being able to recover all of those single cells for analysis. Our data supports the recommendation to use stereology, not flow cytometry, to accurately estimate the number of a particular cell-type in solid tissue. Accurate estimation of the absolute number of a particular cell-type in whole organs is increasingly important in studies on organogenesis, and the remodelling and repair of diseased tissues. Although estimation of the relative number of cells might be straightforward, unbiased estimation of the absolute number of cells in an organ is complicated, and design-based stereology remains the method of choice. This has led investigators to explore alternative approaches - such as flow cytometry - as a faster and less labour-intensive replacement for stereology. To address whether flow cytometry might substitute stereology, design-based stereology was compared with microfluorosphere-controlled flow cytometry, for estimation of the absolute number of alveolar epithelial type 2 cells (AEC2) in the lungs of two mouse strains: wild-type C57BL/6J mice and Sftpc-YFP mice. Using design-based stereology, ≈10.7 million and ≈9.0 million AEC2 were estimated in the lungs of wild-type C57BL/6J mice and Sftpc-YFP mice, respectively. Substantially fewer AEC2 were estimated using flow cytometry. In wild-type C57/BL6J mouse lungs, 59% of the AEC2 estimated by design-based stereology were estimated by flow cytometry (≈6.3 million), using intracellular staining for pro-surfactant protein C. Similarly, in Sftpc-YFP mouse lungs, 23% of the AEC2 estimated by design-based stereology were estimated by flow cytometry (≈2.1 million), using yellow fluorescent protein fluorescence. Our data suggest that flow cytometry underestimates AEC2 number, possibly due to impaired recoverability of AEC2 from dissociated lung tissue. These data suggest design-based stereology as the method of choice for the unbiased estimation of the absolute number of cells in an organ.
- Published
- 2018
9. A novel mouse Cre-driver line targeting Perilipin 2-expressing cells in the neonatal lung
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Robert Voswinckel, Thomas Braun, Elie El Agha, Saverio Bellusci, Jennifer Quantius, Marten Szibor, Susanne Herold, José Alberto Rodríguez-Castillo, Werner Seeger, Aglaia Ntokou, Katrin Ahlbrecht, Isabelle Salwig, and Rory E. Morty
- Subjects
0301 basic medicine ,Perilipin 2 ,Cellular differentiation ,Organogenesis ,Spleen ,Perilipin-2 ,03 medical and health sciences ,Mice ,Endocrinology ,Gene knockin ,Genetics ,medicine ,Animals ,Progenitor cell ,Lung ,biology ,Integrases ,Mesenchymal stem cell ,Cell Differentiation ,Epithelial Cells ,Cell Biology ,respiratory system ,Fibroblasts ,Pulmonary Alveoli ,030104 developmental biology ,medicine.anatomical_structure ,Immunology ,biology.protein ,Cancer research ,Myofibroblast - Abstract
Pulmonary diseases such as chronic obstructive pulmonary disease, lung fibrosis, and bronchopulmonary dysplasia are characterized by the destruction or malformation of the alveolar regions of the lung. The underlying pathomechanisms at play are an area of intense interest since these mechanisms may reveal pathways suitable for interventions to drive reparative processes. Lipid-laden fibroblasts (lipofibroblasts) express the Perilipin 2 (Plin2) gene-product, PLIN2, commonly called adipose-differentiation related protein (ADRP). These cells are also thought to play a role in alveolarization and repair after injury to the alveolus. Progress in defining the functional contribution of lipofibroblasts to alveolar generation and repair is hampered by a lack of in vivo tools. The present study reports the generation of an inducible mouse Cre-driver line to target cells of the ADRP lineage. Robust Cre-mediated recombination in this mouse line was detected in mesenchymal cells of the postnatal lung, and in additional organs including the heart, liver, and spleen. The generation and validation of this valuable new tool to genetically target, manipulate, and trace cells of the ADRP lineage is critical for assessing the functional contribution of lipofibroblasts to lung development and repair.
- Published
- 2017
10. Broad AOX expression in a genetically tractable mouse model does not disturb normal physiology
- Author
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Kira M. Holmström, Valerie Gailus-Durner, Martin Hrabě de Angelis, Howard T. Jacobs, Eric Dufour, Ilka Wittig, Jatin Nandania, Marten Szibor, T. M. Gainutdinov, Pierre Rustin, Thomas Braun, Isabelle Salwig, Frank N. Gellerich, Juliana Heidler, Yuan Zhuang, Vidya Velagapudi, Zemfira Gizatullina, Helmut Fuchs, Astrid Wietelmann, Praveen K. Dhandapani, Institute of Biotechnology, Institute for Molecular Medicine Finland, Lääketieteen ja biotieteiden tiedekunta - Faculty of Medicine and Life Sciences, University of Tampere, and German Mouse Clinic Consortium
- Subjects
0301 basic medicine ,RNA, Untranslated ,Respiratory chain ,Medicine (miscellaneous) ,Physiology ,lcsh:Medicine ,ALTERNATIVE-OXIDASE ,Mitochondrion ,Immunology and Microbiology (miscellaneous) ,Mitochondria ,Mitochondrial disease ,Alternative oxidase ,Physiological Phenomena ,Plant Proteins ,ACUTE LETHALITY ,biology ,DEFECTS ,Ciona intestinalis ,DEFICIENCY ,DROSOPHILA ,Mitochondrial respiratory chain ,NATIVE ELECTROPHORESIS ,Biochemistry ,Oxidoreductases ,Research Article ,lcsh:RB1-214 ,Biolääketieteet - Biomedicine ,Transgene ,Mitochondrial Disease ,Respiratory Chain ,Alternative Oxidase ,Neuroscience (miscellaneous) ,Mice, Transgenic ,Protective Agents ,General Biochemistry, Genetics and Molecular Biology ,Mitochondrial Proteins ,PROTEIN COMPLEXES ,03 medical and health sciences ,medicine ,Metabolome ,lcsh:Pathology ,Animals ,ddc:610 ,Cyanides ,HUMAN-CELLS ,lcsh:R ,biology.organism_classification ,medicine.disease ,MICE ,030104 developmental biology ,1182 Biochemistry, cell and molecular biology ,3111 Biomedicine - Abstract
Plants and many lower organisms, but not mammals, express alternative oxidases (AOXs) that branch the mitochondrial respiratory chain, transferring electrons directly from ubiquinol to oxygen without proton pumping. Thus, they maintain electron flow under conditions when the classical respiratory chain is impaired, limiting excess production of oxygen radicals and supporting redox and metabolic homeostasis. AOX from Ciona intestinalis has been used to study and mitigate mitochondrial impairments in mammalian cell lines, Drosophila disease models and, most recently, in the mouse, where multiple lentivector-AOX transgenes conferred substantial expression in specific tissues. Here, we describe a genetically tractable mouse model in which Ciona AOX has been targeted to the Rosa26 locus for ubiquitous expression. The AOXRosa26 mouse exhibited only subtle phenotypic effects on respiratory complex formation, oxygen consumption or the global metabolome, and showed an essentially normal physiology. AOX conferred robust resistance to inhibitors of the respiratory chain in organello; moreover, animals exposed to a systemically applied LD50 dose of cyanide did not succumb. The AOXRosa26 mouse is a useful tool to investigate respiratory control mechanisms and to decipher mitochondrial disease aetiology in vivo., Summary: Previous limitations are overcome in this first genetically tractable mouse model expressing invertebrate alternative oxidase, AOX, which can suppress pathological stresses in the mitochondrial respiratory chain.
- Published
- 2017
11. Generation of Clara cells from murine pluripotent stem cells – a new tool to explore airway epithelial regeneration
- Author
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Tobias Cantz, Marcus A. Mall, Malte Sgodda, Sabrina Schmeckebier, T Braus, Julia Duerr, Christina Mauritz, Verena Puppe, K. Katsirntaki, SC Schuber, Ulrich Martin, Isabelle Salwig, Andreas Schmiedl, Marten Szibor, Reto Eggenschwiler, and Matthias Ochs
- Subjects
Pulmonary and Respiratory Medicine ,Regeneration (biology) ,Biology ,Induced pluripotent stem cell ,Airway ,Cell biology - Published
- 2014
12. Identification and characterization of Bronchioalveolar stem cells
- Author
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Marten Szibor, HR Schöler, Werner Seeger, Isabelle Salwig, C Koumba, and Robert Voswinckel
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Pulmonary and Respiratory Medicine ,Identification (biology) ,Computational biology ,Stem cell ,Biology - Published
- 2012
13. Genetic targeting of Clara cells using a novel knock-in strategy
- Author
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Isabelle Salwig, Marten Szibor, and Thomas Braun
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Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Gene knockin ,medicine ,Biology ,Cell biology - Published
- 2012
14. Induction of smooth muscle cell migration during arteriogenesis is mediated by Rap2
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Jaeyoung Shin, Jochen Pöling, Isabelle Salwig, Silvia Schimanski, Marten Szibor, Holger Lörchner, W. Rees, Thomas Kubin, K Wiebe, Thomas Braun, Henning Warnecke, Praveen Gajawada, Zaber Kochfar, and Marie-Elisabeth Ingelmann
- Subjects
Vascular smooth muscle ,Time Factors ,Smooth muscle cell migration ,Myocytes, Smooth Muscle ,Collateral Circulation ,Neovascularization, Physiologic ,Arterial Occlusive Diseases ,Biology ,Fibroblast growth factor ,Transfection ,Muscle, Smooth, Vascular ,Mice ,Downregulation and upregulation ,Cell Movement ,Myocyte ,Animals ,Humans ,Receptor, Fibroblast Growth Factor, Type 1 ,Ligation ,Cell Proliferation ,Cell growth ,Fibroblast growth factor receptor 1 ,Anatomy ,Cell biology ,Femoral Artery ,Disease Models, Animal ,HEK293 Cells ,rap GTP-Binding Proteins ,Regional Blood Flow ,Fibroblast Growth Factor 2 ,RNA Interference ,Arteriogenesis ,Rabbits ,Cardiology and Cardiovascular Medicine - Abstract
Objective— Collateral artery growth or arteriogenesis is the primary means of the circulatory system to maintain blood flow in the face of major arterial occlusions. Arteriogenesis depends on activation of fibroblast growth factor (FGF) receptors, but relatively little is known about downstream mediators of FGF signaling. Methods and Results— We screened for signaling components that are activated in response to administration of FGF-2 to cultured vascular smooth muscle cells (VSMCs) and detected a significant increase of Rap2 but not of other Ras family members, which corresponded to a strong upregulation of Rap2 and C-Raf in growing collaterals from rabbits with femoral artery occlusion. Small interfering RNAs directed against Rap2 did not affect FGF-2 induced proliferation of VSMC but strongly inhibited their migration. Inhibition of FGF receptor-1 (FGFR1) signaling by infusion of a sulfonic acid polymer or infection with a dominant-negative FGFR1 adenovirus inhibited Rap2 upregulation and collateral vessel growth. Similarly, expression of dominant-negative Rap2 blocked arteriogenesis, whereas constitutive active Rap2 enhanced collateral vessel growth. Conclusion— Rap2 is part of the arteriogenic program and acts downstream of the FGFR1 to stimulate VSMC migration. Specific modulation of Rap2 might be an attractive target to manipulate VSMC migration, which plays a role in numerous pathological processes.
- Published
- 2011
15. Nitric oxide-associated protein 1 (NOA1) is necessary for oxygen-dependent regulation of mitochondrial respiratory complexes
- Author
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Isabelle Salwig, Marten Szibor, Thomas Braun, Peter Seibel, Marie-Elisabeth Ingelmann, Christian Kukat, Natalie Al-Furoukh, Jürgen Holtz, Marcus Krüger, Ilka Wittig, and Juliana Heidler
- Subjects
Bioenergetics ,Respiratory chain ,Oxidative phosphorylation ,Mitochondrion ,Biology ,Biochemistry ,Oxidative Phosphorylation ,Nitric oxide ,GTP Phosphohydrolases ,Electron Transport ,Electron Transport Complex IV ,Mitochondrial Proteins ,chemistry.chemical_compound ,Mice ,Oxygen Consumption ,Animals ,Humans ,Prohibitin ,Molecular Biology ,Electron Transport Complex I ,Cell Biology ,Cell biology ,Oxygen ,HEK293 Cells ,chemistry ,Mitochondrial matrix ,NIH 3T3 Cells ,HeLa Cells - Abstract
In eukaryotic cells, maintenance of cellular ATP stores depends mainly on mitochondrial oxidative phosphorylation (OXPHOS), which in turn requires sufficient cellular oxygenation. The crucial role of proper oxygenation for cellular viability is reflected by involvement of several mechanisms, which sense hypoxia and regulate activities of respiratory complexes according to available oxygen concentrations. Here, we focus on mouse nitric oxide-associated protein 1 (mNOA1), which has been identified as an important component of the machinery that adjusts OXPHOS activity to oxygen concentrations. mNOA1 is an evolutionary conserved GTP-binding protein that is involved in the regulation of mitochondrial protein translation and respiration. We found that mNOA1 is located mostly in the mitochondrial matrix from where it interacts with several high molecular mass complexes, most notably with the complex IV of the respiratory chain and the prohibitin complex. Knock-down of mNOA1 impaired enzyme activity I+III, resulting in oxidative stress and eventually cell death. mNOA1 is transcriptionally regulated in an oxygen-sensitive manner. We propose that oxygen-dependent regulation of mNOA1 is instrumental to adjusting OXPHOS activity to oxygen availability, thereby controlling mitochondrial metabolism.
- Published
- 2011
16. Solvent-Induced Chirality in the Hydroboration of Ketones
- Author
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Nina Dickerhof, Isabelle Salwig, Christoph Baldauf, Friedrich Kruse, Birgit Spitznagel, Janine May, Stefanie Kern, Nico Scharfenecker, Melanie Meister, Kristina Müller, Nancy Krummrich, Stefan H. Hüttenhain, and Sabine Rauer
- Subjects
Solvent ,chemistry.chemical_compound ,Hydroboration ,chemistry ,Biocatalysis ,Organic chemistry ,General Chemistry ,Lewis acids and bases ,Enantiomeric excess ,Chirality (chemistry) ,Asymmetric induction ,Acetophenone - Abstract
The influence of the systematic variation of chiral solvents and of diverse Lewis acids on the asymmetric induction of the hydroboration of acetophenone has been studied. None of the solvents used could surpass lactic acid methyl ester, and for the Lewis acids, ZnCl2 and ZnI2 showed positive effects on the enantiomeric excess (ee) and the conversion. Also, the effect of the substrate structure was investigated by comparing the conversion and ee of eight different ketones. Apparently, the achievable asymmetric induction was higher with aromatic ketones.
- Published
- 2008
17. Solvent-Induced Chirality in the Hydroboration of Ketones.
- Author
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Christoph Baldauf, Nina Dickerhof, Stefan H. Httenhain, Stefanie Kern, Nancy Krummrich, Friedrich Kruse, Janine May, Melanie Meister, Kristina Mller, Sabine Rauer, Isabelle Salwig, Nico Scharfenecker, and Birgit Spitznagel
- Abstract
The influence of the systematic variation of chiral solvents and of diverse Lewis acids on the asymmetric induction of the hydroboration of acetophenone has been studied. None of the solvents used could surpass lactic acid methyl ester, and for the Lewis acids, ZnCl2 and ZnI2 showed positive effects on the enantiomeric excess (ee) and the conversion. Also, the effect of the substrate structure was investigated by comparing the conversion and ee of eight different ketones. Apparently, the achievable asymmetric induction was higher with aromatic ketones. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
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