127 results on '"Hélène Gilgenkrantz"'
Search Results
2. Monoacylglycerol lipase reprograms hepatocytes and macrophages to promote liver regeneration
- Author
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Manon Allaire, Rola Al Sayegh, Morgane Mabire, Adel Hammoutene, Matthieu Siebert, Charles Caër, Mathilde Cadoux, JingHong Wan, Aida Habib, Maude Le Gall, Pierre de la Grange, Hervé Guillou, Catherine Postic, Valérie Paradis, Sophie Lotersztajn, and Hélène Gilgenkrantz
- Subjects
Wound healing ,Injury ,MAGL ,Proliferation ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: Liver regeneration is a repair process in which metabolic reprogramming of parenchymal and inflammatory cells plays a major role. Monoacylglycerol lipase (MAGL) is an ubiquitous enzyme at the crossroad between lipid metabolism and inflammation. It converts monoacylglycerols into free fatty acids and metabolises 2-arachidonoylglycerol into arachidonic acid, being thus the major source of pro-inflammatory prostaglandins in the liver. In this study, we investigated the role of MAGL in liver regeneration. Methods: Hepatocyte proliferation was studied in vitro in hepatoma cell lines and ex vivo in precision-cut human liver slices. Liver regeneration was investigated in mice treated with a pharmacological MAGL inhibitor, MJN110, as well as in animals globally invalidated for MAGL (MAGL-/-) and specifically invalidated in hepatocytes (MAGLHep-/-) or myeloid cells (MAGLMye-/-). Two models of liver regeneration were used: acute toxic carbon tetrachloride injection and two-thirds partial hepatectomy. MAGLMye-/- liver macrophages profiling was analysed by RNA sequencing. A rescue experiment was performed by in vivo administration of interferon receptor antibody in MAGLMye-/- mice. Results: Precision-cut human liver slices from patients with chronic liver disease and human hepatocyte cell lines exposed to MJN110 showed reduced hepatocyte proliferation. Mice with global invalidation or mice treated with MJN110 showed blunted liver regeneration. Moreover, mice with specific deletion of MAGL in either hepatocytes or myeloid cells displayed delayed liver regeneration. Mechanistically, MAGLHep-/- mice showed reduced liver eicosanoid production, in particular prostaglandin E2 that negatively impacts on hepatocyte proliferation. MAGL inhibition in macrophages resulted in the induction of the type I interferon pathway. Importantly, neutralising the type I interferon pathway restored liver regeneration of MAGLMye-/- mice. Conclusions: Our data demonstrate that MAGL promotes liver regeneration by hepatocyte and macrophage reprogramming. Impact and Implications: By using human liver samples and mouse models of global or specific cell type invalidation, we show that the monoacylglycerol pathway plays an essential role in liver regeneration. We unveil the mechanisms by which MAGL expressed in both hepatocytes and macrophages impacts the liver regeneration process, via eicosanoid production by hepatocytes and the modulation of the macrophage interferon pathway profile that restrains hepatocyte proliferation.
- Published
- 2023
- Full Text
- View/download PDF
3. Mucosal-associated invariant T cells are a profibrogenic immune cell population in the liver
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Pushpa Hegde, Emmanuel Weiss, Valérie Paradis, Jinghong Wan, Morgane Mabire, Sukriti Sukriti, Pierre-Emmanuel Rautou, Miguel Albuquerque, Olivia Picq, Abhishak Chandra Gupta, Gladys Ferrere, Hélène Gilgenkrantz, Badr Kiaf, Amine Toubal, Lucie Beaudoin, Philippe Lettéron, Richard Moreau, Agnès Lehuen, and Sophie Lotersztajn
- Subjects
Science - Abstract
Hepatic fibrosis represents the liver response to chronic injury and can lead to cirrhosis. Here the authors show that mucosal-associated invariant T cells mediate chronic inflammation and fibrogenesis in the liver by inducing a proinflammatory phenotype in macrophages and myofibroblasts and proliferation of the latter.
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- 2018
- Full Text
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4. Pre-therapy liver transcriptome landscape in Indian and French patients with severe alcoholic hepatitis and steroid responsiveness
- Author
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Shvetank Sharma, Jaswinder S. Maras, Sukanta Das, Shabir Hussain, Ashwani K. Mishra, Saggere M. Shasthry, Chhagan B. Sharma, Emmanuel Weiss, Laure Elkrief, Pierre-Emmanuel Rautou, Hélène Gilgenkrantz, Sophie Lotersztajn, Valérie Paradis, Pierre de la Grange, Christophe Junot, Richard Moreau, and Shiv K. Sarin
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Medicine ,Science - Abstract
Abstract Patients with severe alcoholic hepatitis (SAH) not responding to glucocorticoid therapy have higher mortality, though they do not differ in their baseline clinical characteristics and prognostic scores from those who respond to therapy. We hypothesized that the baseline hepatic gene expression differs between responders (R) and non-responders (NR). Baseline liver transcriptome was compared between R and NR in Indian (16 each) and French (5 NR, 3 R) patients with SAH. There were differentially expressed genes (DEGs) between NR and R, in Indian (1106 over-expressed, 96 under-expressed genes) and French patients (65 over-expressed, 142 under-expressed genes). Indian NR had features of hepatocyte senescence and French NR exhibited under-expression of genes involved in cell division, indicating a central defect in the capacity of hepatocytes for self-renewal in both populations. Markers of hepatic progenitor cell proliferation were either very few (Indian patients) or absent (French patients). No DEGs were enriched in inflammatory pathways and there were no differences in nuclear receptor subfamily 3 group C member 1 (NR3C1) transcript expression and splicing between NR and R. Our results reveal that baseline hepatic transcriptome is reflective of subsequent glucocorticoid non-response and indicate impaired regenerative potential of the liver as an underlying phenomenon in NR.
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- 2017
- Full Text
- View/download PDF
5. LKB1 and Notch Pathways Interact and Control Biliary Morphogenesis.
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Pierre-Alexandre Just, Alexis Poncy, Sara Charawi, Rajae Dahmani, Massiré Traore, Typhanie Dumontet, Valérie Drouet, Florent Dumont, Hélène Gilgenkrantz, Sabine Colnot, Benoit Terris, Cédric Coulouarn, Frédéric Lemaigre, and Christine Perret
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Medicine ,Science - Abstract
LKB1 is an evolutionary conserved kinase implicated in a wide range of cellular functions including inhibition of cell proliferation, regulation of cell polarity and metabolism. When Lkb1 is inactivated in the liver, glucose homeostasis is perturbed, cellular polarity is affected and cholestasis develops. Cholestasis occurs as a result from deficient bile duct development, yet how LKB1 impacts on biliary morphogenesis is unknown.We characterized the phenotype of mice in which deletion of the Lkb1 gene has been specifically targeted to the hepatoblasts. Our results confirmed that lack of LKB1 in the liver results in bile duct paucity leading to cholestasis. Immunostaining analysis at a prenatal stage showed that LKB1 is not required for differentiation of hepatoblasts to cholangiocyte precursors but promotes maturation of the primitive ductal structures to mature bile ducts. This phenotype is similar to that obtained upon inactivation of Notch signaling in the liver. We tested the hypothesis of a functional overlap between the LKB1 and Notch pathways by gene expression profiling of livers deficient in Lkb1 or in the Notch mediator RbpJκ and identified a mutual cross-talk between LKB1 and Notch signaling. In vitro experiments confirmed that Notch activity was deficient upon LKB1 loss.LKB1 and Notch share a common genetic program in the liver, and regulate bile duct morphogenesis.
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- 2015
- Full Text
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6. EGFR: A Master Piece in G1/S Phase Transition of Liver Regeneration
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Alexandra Collin de l'Hortet, Hélène Gilgenkrantz, and Jacques-Emmanuel Guidotti
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Unraveling the molecular clues of liver proliferation has become conceivable thanks to the model of two-third hepatectomy. The synchronicity and the well-scheduled aspect of this process allow scientists to slowly decipher this mystery. During this phenomenon, quiescent hepatocytes of the remnant lobes are able to reenter into the cell cycle initiating the G1-S progression synchronously before completing the cell cycle. The major role played by this step of the cell cycle has been emphasized by loss-of-function studies showing a delay or a lack of coordination in the hepatocytes G1-S progression. Two growth factor receptors, c-Met and EGFR, tightly drive this transition. Due to the level of complexity surrounding EGFR signaling, involving numerous ligands, highly controlled regulations and multiple downstream pathways, we chose to focus on the EGFR pathway for this paper. We will first describe the EGFR pathway in its integrity and then address its essential role in the G1/S phase transition for hepatocyte proliferation. Recently, other levels of control have been discovered to monitor this pathway, which will lead us to discuss regulations of the EGFR pathway and highlight the potential effect of misregulations in pathologies.
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- 2012
- Full Text
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7. Cell metabolism-based therapy for liver fibrosis, repair and hepatocellular carcinoma
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Hélène Gilgenkrantz, Valérie Paradis, and Sophie Lotersztajn
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Hepatology - Published
- 2023
8. On n’a ni l’âge de ses artères, ni celui de son foie…
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Hélène Gilgenkrantz
- Subjects
General Medicine ,General Biochemistry, Genetics and Molecular Biology - Published
- 2022
9. Axel Kahn à l’ère de la thérapie génique Les années 1980-2000
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Hélène Gilgenkrantz
- Subjects
General Medicine ,General Biochemistry, Genetics and Molecular Biology - Published
- 2021
10. Targeting cell-intrinsic metabolism for antifibrotic therapy
- Author
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Richard Moreau, Hélène Gilgenkrantz, Ariane Mallat, and Sophie Lotersztajn
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Liver Cirrhosis ,Cell ,Immune system ,Non-alcoholic Fatty Liver Disease ,Fibrosis ,Hepatic Stellate Cells ,medicine ,Animals ,Humans ,Lymphocytes ,Hepatology ,business.industry ,Lipogenesis ,Macrophages ,Autophagy ,Lipid metabolism ,medicine.disease ,Phenotype ,Cholesterol ,medicine.anatomical_structure ,Nuclear receptor ,Hepatocytes ,Hepatic stellate cell ,Cancer research ,Antifibrotic Agents ,business ,Glycolysis ,Signal Transduction - Abstract
Summary In recent years, there have been major advances in our understanding of the mechanisms underlying fibrosis progression and regression, and how coordinated interactions between parenchymal and non-parenchymal cells impact on the fibrogenic process. Recent studies have highlighted that metabolic reprogramming of parenchymal cells, immune cells (immunometabolism) and hepatic stellate cells is required to support the energetic and anabolic demands of phenotypic changes and effector functions. In this review, we summarise how targeting cell-intrinsic metabolic modifications of the main fibrogenic cell actors may impact on fibrosis progression and we discuss the antifibrogenic potential of metabolically targeted interventions.
- Published
- 2021
11. The aged liver: Beyond cellular senescence
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Manon Allaire, Hélène Gilgenkrantz, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and CCSD, Accord Elsevier
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Aging ,[SDV]Life Sciences [q-bio] ,medicine.medical_treatment ,Population ,Inflammation ,Liver transplantation ,Bioinformatics ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Autophagy ,medicine ,Homeostasis ,Humans ,Regeneration ,education ,Cellular Senescence ,Aged ,Transplantation ,education.field_of_study ,Hepatology ,business.industry ,Liver Diseases ,Regeneration (biology) ,Gastroenterology ,3. Good health ,[SDV] Life Sciences [q-bio] ,Ageing ,Metabolism ,Liver ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,medicine.symptom ,business - Abstract
International audience; The aging of the population, the increased prevalence of chronic liver diseases in elderly and the need to broaden the list of potential liver donors enjoin us to better understand what is an aged liver. In this review, we provide a brief introduction to cellular senescence, revisit the main morphological and functional modifications of the liver induced by aging, particularly concerning metabolism, immune response and regeneration, and try to elude some of the signalling pathways responsible for these modifications. Finally, we discuss the clinical consequences of aging on chronic liver diseases and the implications of older age for donors and recipients in liver transplantation.
- Published
- 2020
12. Monoacylglycerol lipase inhibition specifically in macrophages compromises liver regeneration by inducing interferon type 1 that negatively impacts on hepatocyte proliferation
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Manon Allaire, Rola Al-Sayegh, Morgane Mabire, Matthieu Siebert, Mathilde Cadoux, JingHong Wan, Maude Le Gall, Catherine Postic, Hervé Guillou, Pierre de la Grange, Sophie Lotersztajn, Hélène Gilgenkrantz, and LESUR, Hélène
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[SDV] Life Sciences [q-bio] ,[SDV.TOX] Life Sciences [q-bio]/Toxicology ,Hepatology - Abstract
Meeting AbstractOS084
- Published
- 2022
13. [What about good in all this? A human passion]
- Author
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Hélène, Gilgenkrantz
- Subjects
Emotions ,Humans - Abstract
Et le Bien dans tout ça ? (Axel Kahn) - Une passion humaine.Cette recension a été écrite avant le décès d’Axel Kahn survenu le 6 juillet 2021. Axel interrogeait le monde avec une curiosité gourmande et une passion communicative. Cet ouvrage aura été son dernier questionnement. Puissent ses lecteurs continuer de se poser la question….
- Published
- 2021
14. LC3-associated phagocytosis in myeloid cells, a fireman that restrains inflammation and liver fibrosis, via immunoreceptor inhibitory signaling
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Pierre-Marie Choinier, Linda Broer, Jinghong Wan, Marcelle Bens, Emmanuel Weiss, Morgane Mabire, Sanae Ben Mkaddem, Sophie Lotersztajn, Patrice Codogno, Richard Moreau, Renato C. Monteiro, Tristan Thibault-Sogorb, Loredana Saveanu, Pushpa Hegde, and Hélène Gilgenkrantz
- Subjects
Liver Cirrhosis ,0301 basic medicine ,Cirrhosis ,Phagocytosis ,Inflammation ,Biology ,Systemic inflammation ,03 medical and health sciences ,Liver disease ,medicine ,Humans ,Macrophage ,Myeloid Cells ,Molecular Biology ,030102 biochemistry & molecular biology ,Monocyte ,digestive, oral, and skin physiology ,Autophagy ,Cell Biology ,medicine.disease ,Autophagic Punctum ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,Cancer research ,medicine.symptom ,Microtubule-Associated Proteins ,human activities ,Signal Transduction - Abstract
Control of systemic and hepatic inflammation, in particular originating from monocytes/macrophages, is crucial to prevent liver fibrosis and its progression to end-stage cirrhosis. LC3-associated phagocytosis (LAP) is a non-canonical form of autophagy that shifts the monocyte/macrophage phenotype to an anti-inflammatory phenotype. In a recent study, we uncovered LAP as a protective mechanism against inflammation-driven liver fibrosis and systemic inflammation in the context of cirrhosis. We observed that LAP is enhanced in blood and liver monocytes from patients with liver fibrosis or those who progress to cirrhosis. Combining studies in which LAP was pharmacologically or genetically inactivated, we found that LAP limits inflammation in monocytes from cirrhotic patients, and the hepatic inflammatory profile in mice with chronic liver injury, resulting in anti-fibrogenic effects. Mechanistically, LAP-induced anti-inflammatory and antifibrogenic signaling results from enhanced expression of the Fc immunoreceptor FCGR2A/FcγRIIA and activation of an FCGR2A-mediated PTPN6/SHP-1 anti-inflammatory pathway, leading to increased engulfment of IgG into LC3 (+) phagosomes. In patients with cirrhosis progressing to multi-organ failure (acute-on chronic liver failure), LAP is lost in monocytes, and can be restored by targeting FCGR2A-mediated PTPN6/SHP-1 signaling. These data suggest that sustaining LAP may open novel therapeutic perspectives for patients with end-stage liver disease.
- Published
- 2020
15. L’émergence des modèles miniatures de foie gras humain en 3D générés en laboratoire
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Hélène Gilgenkrantz and Alexandra Collin de l'Hortet
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Liver injury ,Triglyceride ,business.industry ,Fatty liver ,Inflammation ,General Medicine ,medicine.disease ,Bioinformatics ,General Biochemistry, Genetics and Molecular Biology ,chemistry.chemical_compound ,chemistry ,Fibrosis ,Nonalcoholic fatty liver disease ,medicine ,medicine.symptom ,business ,Induced pluripotent stem cell ,Liver pathology - Abstract
Les organoïdes constituent une approche de choix pour modéliser a minima une maladie humaine et tester l’efficacité thérapeutique de certaines drogues. La stéatopathie métabolique ou maladie du foie gras, dont l’incidence a considérablement augmenté avec l’accroissement de l’obésité dans les pays développés, se caractérise par l’accumulation de triglycerides dans l’hépatocyte et une atteinte hépatique pouvant évoluer vers la fibrose. Il n’existe pas de traitement efficace, mais de nombreuses pistes sont actuellement explorées. Deux équipes américaines ont récemment utilisé les cellules souches pluripotentes induites (iPS) et la culture muticellulaire pour modéliser un mini-foie stéatosique par deux approches différentes, offrant ainsi de nouveaux outils pour tester les drogues en cours de développement.
- Published
- 2020
16. Age and liver transplantation
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Hélène Gilgenkrantz, Olivier Soubrane, François Cauchy, Josh Levitsky, François Durand, Claire Francoz, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Paris Diderot - Paris 7 (UPD7)
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Adult ,Male ,0301 basic medicine ,Aging ,Brain Death ,Matching (statistics) ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Waiting Lists ,[SDV]Life Sciences [q-bio] ,medicine.medical_treatment ,Transplants ,Liver transplantation ,Donor Selection ,Young Adult ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Risk Factors ,Transplanted liver ,Cadaver ,Living Donors ,Humans ,Medicine ,Aged ,Aged, 80 and over ,Hepatology ,business.industry ,Graft Survival ,Age Factors ,Immunosuppression ,Middle Aged ,medicine.disease ,Transplant Recipients ,Liver Transplantation ,3. Good health ,030104 developmental biology ,Donation ,Cohort ,Female ,030211 gastroenterology & hepatology ,Living donor liver transplantation ,business - Abstract
The average age of liver transplant donors and recipients has increased over the years. Independent of the cause of liver disease, older candidates have more comorbidities, higher waitlist mortality and higher post-transplant mortality than younger patients. However, transplant benefit may be similar in older and younger recipients, provided older recipients are carefully selected. The cohort of elderly patients transplanted decades ago is also increasingly raising issues concerning long-term exposure to immunosuppression and aging of the transplanted liver. Excellent results can be achieved with elderly donors and there is virtually no upper age limit for donors after brain death liver transplantation. The issue is how to optimise selection, procurement and matching to ensure good results with elderly donors. The impact of old donor age is more pronounced in younger recipients and patients with a high model for end-stage liver disease score. Age matching between the donor and the recipient should be incorporated into allocation policies with a multistep approach. However, age matching may vary depending on the objectives of different allocation policies. In addition, age matching must be revisited in the era of direct-acting antivirals. More restrictive limits have been adopted in donation after circulatory death. Perfusion machines which are currently under investigation may help expand these limits. In living donor liver transplantation, donor age limit is essentially guided by morbidity related to procurement. In this review we summarise changing trends in recipient and donor age. We discuss the implications of older age donors and recipients. We also consider different options for age matching in liver transplantation that could improve outcomes.
- Published
- 2019
17. Et le Bien dans tout ça ? (Axel Kahn)
- Author
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Hélène Gilgenkrantz
- Subjects
0303 health sciences ,03 medical and health sciences ,0302 clinical medicine ,General Medicine ,030217 neurology & neurosurgery ,General Biochemistry, Genetics and Molecular Biology ,030304 developmental biology - Abstract
Cette recension a été écrite avant le décès d’Axel Kahn survenu le 6 juillet 2021. Axel interrogeait le monde avec une curiosité gourmande et une passion communicative. Cet ouvrage aura été son dernier questionnement. Puissent ses lecteurs continuer de se poser la question…
- Published
- 2021
18. MAIT cell inhibition promotes liver fibrosis regression by reprogramming macrophage phenotype
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Morgane Mabire, Hegde Pushpa, Hammoutene Adel, JingHong Wan, Manon Allaire, Al Sayegh Rola, Tristan Thibault-Sogorb, Emmanuel Weiss, Valérie Paradis, Pierre de la Grange, Hélène Gilgenkrantz, and Sophie Lotersztajn
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Hepatology - Published
- 2022
19. LC3-associated phagocytosis protects against inflammation and liver fibrosis via immunoreceptor inhibitory signaling
- Author
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Tristan Thibault-Sogorb, Pierre-Marie Choinier, Jinghong Wan, Linda Broer, Sanae Ben Mkaddem, Patrice Codogno, Richard Moreau, Emmanuel Weiss, Sophie Lotersztajn, Olivia Picq, Loredana Saveanu, Dorsa Pishvaie, Marcelle Bens, Morgane Mabire, Pushpa Hegde, Hélène Gilgenkrantz, and Renato C. Monteiro
- Subjects
Liver Cirrhosis ,Cirrhosis ,Phagocytosis ,Inflammation ,Chronic liver disease ,Systemic inflammation ,Immunoglobulin G ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Fibrosis ,medicine ,Animals ,Humans ,030304 developmental biology ,0303 health sciences ,biology ,business.industry ,Monocyte ,General Medicine ,medicine.disease ,3. Good health ,Mice, Inbred C57BL ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,medicine.symptom ,business ,Microtubule-Associated Proteins ,Signal Transduction - Abstract
Sustained hepatic and systemic inflammation, particularly originating from monocytes/macrophages, is a driving force for fibrosis progression to end-stage cirrhosis and underlies the development of multiorgan failure. Reprogramming monocyte/macrophage phenotype has emerged as a strategy to limit inflammation during chronic liver injury. Here, we report that LC3-associated phagocytosis (LAP), a noncanonical form of autophagy, protects against hepatic and systemic inflammation during chronic liver injury in rodents, with beneficial antifibrogenic effects. LAP is enhanced in blood and liver monocytes from patients with fibrosis and cirrhosis. Pharmacological inhibition of LAP components in human monocytes from patients with cirrhosis or genetic disruption of LAP in mice with chronic liver injury exacerbates both the inflammatory signature in isolated human monocytes and the hepatic inflammatory profile in mice, resulting in enhanced liver fibrosis. Mechanistically, patients with cirrhosis showed increased monocyte expression of Fc fragment of IgG receptor IIA (FcγRIIA) and enhanced engulfment of immunoglobulin G in LC3+ phagosomes that triggers an FcγRIIA/Src homology region 2 domain-containing phosphatase-1 (SHP-1) inhibitory immunoreceptor tyrosine-based activation motif (ITAMi) anti-inflammatory pathway. Mice overexpressing human FcγRIIA in myeloid cells show enhanced LAP in response to chronic liver injury and resistance to inflammation and liver fibrosis. Activation of LAP is lost in monocytes from patients with multiorgan failure and restored by specifically targeting ITAMi signaling with anti-FcγRIIA F(ab')2 fragments, or with intravenous immunoglobulin (IVIg). These data suggest the existence of an ITAMi-mediated mechanism by which LAP might protect against inflammation. Sustaining LAP may open therapeutic perspectives for patients with chronic liver disease.
- Published
- 2020
20. [Emergence of 3D human fatty liver models engineered in the laboratory]
- Author
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Alexandra, Collin de l'Hortet and Hélène, Gilgenkrantz
- Subjects
Liver Cirrhosis ,Tissue Culture Techniques ,Liver ,Tissue Scaffolds ,Non-alcoholic Fatty Liver Disease ,Disease Progression ,Hepatocytes ,Medical Laboratory Science ,Animals ,Humans ,Bioengineering ,Models, Biological ,Cells, Cultured - Abstract
Organoids offer an elegant approach to model human diseases and test new drugs. Nonalcoholic fatty liver disease (NAFLD) whose incidence has dramatically increased in recent years with the rise of obesity, is defined by triglyceride accumulation in hepatocytes, inflammation, liver injury, and progression to fibrosis. There is currently no approved therapy but many pathways are being explored. Two American teams have created mini-steatotic livers using different approaches, both using induced pluripotent stem cells (iPS), thus offering new tools to test developing drugs.L’émergence des modèles miniatures de foie gras humain en 3D générés en laboratoire.Les organoïdes constituent une approche de choix pour modéliser a minima une maladie humaine et tester l’efficacité thérapeutique de certaines drogues. La stéatopathie métabolique ou maladie du foie gras, dont l’incidence a considérablement augmenté avec l’accroissement de l’obésité dans les pays développés, se caractérise par l’accumulation de triglycerides dans l’hépatocyte et une atteinte hépatique pouvant évoluer vers la fibrose. Il n’existe pas de traitement efficace, mais de nombreuses pistes sont actuellement explorées. Deux équipes américaines ont récemment utilisé les cellules souches pluripotentes induites (iPS) et la culture muticellulaire pour modéliser un mini-foie stéatosique par deux approches différentes, offrant ainsi de nouveaux outils pour tester les drogues en cours de développement.
- Published
- 2020
21. Un dialogue précoce indispensable entre cellules MAIT et microbiote
- Author
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Hélène Gilgenkrantz, Institut Cochin (IC UM3 (UMR 8104 / U1016)), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
0303 health sciences ,[SDV]Life Sciences [q-bio] ,MAIT Cells ,General Medicine ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Cell biology ,03 medical and health sciences ,Crosstalk (biology) ,0302 clinical medicine ,030217 neurology & neurosurgery ,Tissue homeostasis ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology - Abstract
International audience; No abstract available
- Published
- 2020
22. Understanding Liver Regeneration
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Alexandra Collin de l'Hortet and Hélène Gilgenkrantz
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0301 basic medicine ,business.industry ,Regeneration (biology) ,Increased fibrosis ,Liver resections ,Regenerative medicine ,Liver regeneration ,Pathology and Forensic Medicine ,Transplantation ,03 medical and health sciences ,030104 developmental biology ,Cancer research ,Medicine ,Hepatocyte dedifferentiation ,Progenitor cell ,business - Abstract
Liver regeneration is a complex and unique process. When two-thirds of a mouse liver is removed, the remaining liver recovers its initial weight in approximately 10 days. The understanding of the mechanisms responsible for liver regeneration may help patients needing large liver resections or transplantation and may be applied to the field of regenerative medicine. All differentiated hepatocytes are capable of self-renewal, but different subpopulations of hepatocytes seem to have distinct proliferative abilities. In the setting of chronic liver diseases, a ductular reaction ensues in which liver progenitor cells (LPCs) proliferate in the periportal region. Although these LPCs have the capacity to differentiate into hepatocytes and biliary cells in vitro, their ability to participate in liver regeneration is far from clear. Their expansion has even been associated with increased fibrosis and poorer prognosis in chronic liver diseases. Controversies also remain on their origin: lineage studies in experimental mouse models of chronic injury have recently suggested that these LPCs originate from hepatocyte dedifferentiation, whereas in other situations, they seem to come from cholangiocytes. This review summarizes data published in the past 5 years in the liver regeneration field, discusses the mechanisms leading to regeneration disruption in chronic liver disorders, and addresses the potential use of novel approaches for regenerative medicine.
- Published
- 2018
23. Antagonistes du récepteur CB1 des cannabinoïdes et obésité
- Author
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Hélène Gilgenkrantz and Sophie Lotersztajn
- Subjects
0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,business.industry ,Medicine ,General Medicine ,business ,General Biochemistry, Genetics and Molecular Biology - Published
- 2018
24. Pre-therapy liver transcriptome landscape in Indian and French patients with severe alcoholic hepatitis and steroid responsiveness
- Author
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Saggere Muralikrishna Shasthry, Emmanuel Weiss, Richard Moreau, Shvetank Sharma, Pierre-Emmanuel Rautou, Shiv Kumar Sarin, Ashwani K. Mishra, Valérie Paradis, Christophe Junot, Pierre de la Grange, C. Sharma, Sukanta Das, Jaswinder Singh Maras, Laure Elkrief, Hélène Gilgenkrantz, S. Hussain, and Sophie Lotersztajn
- Subjects
Adult ,Male ,0301 basic medicine ,Senescence ,medicine.medical_specialty ,Science ,Alcoholic hepatitis ,Biology ,Article ,Transcriptome ,03 medical and health sciences ,Receptors, Glucocorticoid ,Glucocorticoid receptor ,Internal medicine ,Ethnicity ,medicine ,Humans ,Progenitor cell ,Glucocorticoids ,Cell Proliferation ,Multidisciplinary ,Fatty liver ,Middle Aged ,medicine.disease ,3. Good health ,030104 developmental biology ,Endocrinology ,Nuclear receptor ,Immunology ,Hepatocytes ,Medicine ,Female ,Glucocorticoid ,Fatty Liver, Alcoholic ,medicine.drug - Abstract
Patients with severe alcoholic hepatitis (SAH) not responding to glucocorticoid therapy have higher mortality, though they do not differ in their baseline clinical characteristics and prognostic scores from those who respond to therapy. We hypothesized that the baseline hepatic gene expression differs between responders (R) and non-responders (NR). Baseline liver transcriptome was compared between R and NR in Indian (16 each) and French (5 NR, 3 R) patients with SAH. There were differentially expressed genes (DEGs) between NR and R, in Indian (1106 over-expressed, 96 under-expressed genes) and French patients (65 over-expressed, 142 under-expressed genes). Indian NR had features of hepatocyte senescence and French NR exhibited under-expression of genes involved in cell division, indicating a central defect in the capacity of hepatocytes for self-renewal in both populations. Markers of hepatic progenitor cell proliferation were either very few (Indian patients) or absent (French patients). No DEGs were enriched in inflammatory pathways and there were no differences in nuclear receptor subfamily 3 group C member 1 (NR3C1) transcript expression and splicing between NR and R. Our results reveal that baseline hepatic transcriptome is reflective of subsequent glucocorticoid non-response and indicate impaired regenerative potential of the liver as an underlying phenomenon in NR.
- Published
- 2017
25. L’autophagie dans les maladies chroniques du foie
- Author
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Philippe Gual, Hélène Gilgenkrantz, and Sophie Lotersztajn
- Subjects
0301 basic medicine ,Alcoholic liver disease ,business.industry ,Fatty liver ,Cell ,Autophagy ,nutritional and metabolic diseases ,General Medicine ,Disease ,medicine.disease ,Bioinformatics ,General Biochemistry, Genetics and Molecular Biology ,Liver regeneration ,Pathogenesis ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,medicine ,business ,Homeostasis - Abstract
Within recycling damaged cell components, autophagy maintains cell homeostasis. Thus, it has been anticipated that autophagy would play an essential role in the pathogenesis of chronic liver diseases. Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the most prevalent chronic liver diseases in Western countries, sharing common histopathologic features and a common disease progression. In this review, we discuss the role of autophagy at different stages of NAFLD and ALD as well as in liver regeneration and hepatocarcinogenesis.
- Published
- 2017
26. Monoacylglycerol lipase reprograms lipid metabolism in macrophages and hepatocytes to promote liver regeneration
- Author
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Manon Allaire, Matthieu Siebert, Rola Al-Sayegh, Morgane Mabire, JingHong Wan, Benjamin Morin, Maude Le Gall, Sophie Lotersztajn, and Hélène Gilgenkrantz
- Subjects
Hepatology - Published
- 2020
27. β-catenin-activated hepatocellular carcinomas are addicted to fatty acids
- Author
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Nadia Senni, Benoit Terris, David Cabrerizo Granados, Isabelle Lagoutte, Christine Perret, Hélène Gilgenkrantz, Sabine Colnot, Angélique Gougelet, Pascale Bossard, Mathilde Savall, Chiara Sartor, Marie-Clotilde Alves-Guerra, GOUGELET, Angélique, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Anatomie et de cytologie pathologiques [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], and Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,Carcinoma, Hepatocellular ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biology ,Targeted therapy ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Lipid oxidation ,lipid oxidation ,medicine ,Animals ,Humans ,PPAR alpha ,Glycolysis ,Beta oxidation ,beta Catenin ,ComputingMilieux_MISCELLANEOUS ,liver metabolism ,Mice, Knockout ,Fatty Acids ,Liver Neoplasms ,digestive, oral, and skin physiology ,Gastroenterology ,hepatocellular carcinoma ,HCCS ,digestive system diseases ,3. Good health ,Gene Expression Regulation, Neoplastic ,[SDV] Life Sciences [q-bio] ,030104 developmental biology ,chemistry ,Catenin ,Mutation ,Cancer research ,Epoxy Compounds ,030211 gastroenterology & hepatology ,Oxidation-Reduction ,Reprogramming ,Etomoxir - Abstract
ObjectivesCTNNB1-mutated hepatocellular carcinomas (HCCs) constitute a major part of human HCC and are largely inaccessible to target therapy. Yet, little is known about the metabolic reprogramming induced by β-catenin oncogenic activation in the liver. We aimed to decipher such reprogramming and assess whether it may represent a new avenue for targeted therapy of CTNNB1-mutated HCC.DesignWe used mice with hepatocyte-specific oncogenic activation of β-catenin to evaluate metabolic reprogramming using metabolic fluxes on tumourous explants and primary hepatocytes. We assess the role of Pparα in knock-out mice and analysed the consequences of fatty acid oxidation (FAO) using etomoxir. We explored the expression of the FAO pathway in an annotated human HCC dataset.Resultsβ-catenin-activated HCC were not glycolytic but intensively oxidised fatty acids. We found that Pparα is a β-catenin target involved in FAO metabolic reprograming. Deletion of Pparα was sufficient to block the initiation and progression of β-catenin-dependent HCC development. FAO was also enriched in human CTNNB1-mutated HCC, under the control of the transcription factor PPARα.ConclusionsFAO induced by β-catenin oncogenic activation in the liver is the driving force of the β-catenin-induced HCC. Inhibiting FAO by genetic and pharmacological approaches blocks HCC development, showing that inhibition of FAO is a suitable therapeutic approach for CTNNB1-mutated HCC.
- Published
- 2019
28. Non-canonical autophagy in myeloid cells constrains hepatic and systemic inflammation and limits fibrosis
- Author
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JingHong Wan, Emmanuel Weiss, Sanae Ben Mkadden, Morgane Mabire, Pushpa Hegde, Tristan Thibault-Sogorb, Marcelle Bens, Hélène Gilgenkrantz, Richard Moreau, Loredana Saveanu, Patrice Codogno, Renato C Monteiro, and Sophie Lotersztajn
- Subjects
Hepatology - Published
- 2020
29. The impact of steatosis on liver regeneration
- Author
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Manon Allaire and Hélène Gilgenkrantz
- Subjects
0301 basic medicine ,Cirrhosis ,Endocrinology, Diabetes and Metabolism ,Fibroblast growth factor ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Growth factor receptor ,medicine ,Animals ,Humans ,Molecular Biology ,business.industry ,Fatty liver ,General Medicine ,medicine.disease ,Liver regeneration ,Liver Regeneration ,Fatty Liver ,030104 developmental biology ,medicine.anatomical_structure ,Liver ,Hepatocyte ,Cancer research ,030211 gastroenterology & hepatology ,Steatosis ,Steatohepatitis ,business ,Signal Transduction - Abstract
Alcoholic and non-alcoholic fatty liver diseases are the leading causes of cirrhosis in Western countries. These chronic liver diseases share common pathological features ranging from steatosis to steatohepatitis. Fatty liver is associated with primary liver graft dysfunction, a higher incidence of complications/mortality after surgery, in correlation with impaired liver regeneration. Liver regeneration is a multistep process including a priming phase under the control of cytokines followed by a growth factor receptor activation phase leading to hepatocyte proliferation. This process ends when the initial liver mass is restored. Deficiency in epidermal growth factor receptor (EGFR) liver expression, reduced expression of Wee1 and Myt1 kinases, oxidative stress and alteration in hepatocyte macroautophagy have been identified as mechanisms involved in the defective regeneration of fatty livers. Besides the mechanisms, we will also discuss in this review various treatments that have been investigated in the reversal of the regeneration defect, for example, omega-3 fatty acids, pioglitazone, fibroblast growth factor (FGF)19-based chimeric molecule or growth hormone (GH). Since dysbiosis impedes liver regeneration, targeting microbiota could also be an interesting therapeutic approach.
- Published
- 2018
30. [Adipocyte cannabinoid receptor CB1: a relevant target for obesity!]
- Author
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Hélène, Gilgenkrantz and Sophie, Lotersztajn
- Subjects
Male ,Receptor, Cannabinoid, CB2 ,Receptor, Cannabinoid, CB1 ,Adipocytes ,Animals ,Humans ,Female ,Obesity ,Cannabinoid Receptor Antagonists - Published
- 2018
31. AXIN deficiency in human and mouse hepatocytes induces hepatocellular carcinoma in the absence of β-catenin activation
- Author
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Mathilde Savall, Pierre-Alexandre Just, Bernhard Mlecnik, Benoit Terris, Florent Dumont, Mireille Vasseur-Cognet, Valerie Drouet, Pierre Sohier, Romain Sanson, Bruno Ragazzon, Pascale Bossard, Julien Calderaro, Cédric Coulouarn, Hélène Gilgenkrantz, Rajae Dahmani, Emilie Tournier, Shirley Abitbol, Nadia Senni, Jessica Zucman-Rossi, Christine Perret, Ligue Nationale Contre le Cancer - Paris, Ligue Nationale Contre le Cancer (LNCC), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Inovarion, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut d'écologie et des sciences de l'environnement de Paris (iEES), Institut National de la Recherche Agronomique (INRA)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), LNCC (Ligue Nationale Contre le Cancer), Association Francaise pour l'Etude du Foie (AFEF), Ligue Nationnale Contre le Cancer, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Recherche Agronomique (INRA), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Nutrition, Métabolismes et Cancer ( NuMeCan ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Génomique Fonctionnelle des Tumeurs Solides ( U1162 ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut d'écologie et des sciences de l'environnement de Paris ( IEES ), Institut National de la Recherche Agronomique ( INRA ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut d'écologie et des sciences de l'environnement de Paris (IEES (UMR_7618 / UMR_D_242 / UMR_A_1392 / UM_113) ), Institut National de la Recherche Agronomique (INRA)-Sorbonne Université (SU)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Institut d'écologie et des sciences de l'environnement de Paris (IEES), and Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Male ,0301 basic medicine ,Carcinoma, Hepatocellular ,Carcinogenesis ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biology ,medicine.disease_cause ,Mouse model ,Mice ,03 medical and health sciences ,Liver Neoplasms, Experimental ,Axin Protein ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,AXIN1 ,medicine ,Animals ,Humans ,Wnt Signaling Pathway ,neoplasms ,beta Catenin ,Tumor signature ,Cancer ,Mice, Knockout ,Mutation ,Receptors, Notch ,[ SDV ] Life Sciences [q-bio] ,Hepatology ,Liver Neoplasms ,Wnt signaling pathway ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,HCCS ,Prognosis ,medicine.disease ,digestive system diseases ,3. Good health ,Gene expression profiling ,030104 developmental biology ,Liver ,Catenin ,Hepatocytes ,Cancer research - Abstract
Background & Aims The Wnt/β-catenin pathway is the most frequently deregulated pathway in hepatocellular carcinoma (HCC). Inactivating mutations of the gene encoding AXIN1, a known negative regulator of the Wnt/β-catenin signaling pathway, are observed in about 10% of HCCs. Whole-genome studies usually place HCC with AXIN1 mutations and CTNNB1 mutations in the group of tumors with Wnt/β-catenin activated program. However, it has been shown that HCCs with activating CTNNB1 mutations form a group of HCCs, with a different histology, prognosis and genomic signature to those with inactivating biallelic AXIN1 mutations. We aimed to elucidate the relationship between CTNNB1 mutations, AXIN1 mutations and the activation level of the Wnt/β-catenin program. Methods We evaluated two independent human HCC datasets for the expression of a 23-β-catenin target genes program. We modeled Axin1 loss of function tumorigenesis in two engineered mouse models and performed gene expression profiling. Results Based on gene expression, we defined three levels of β-catenin program activation: strong, weak or no activation. While more than 80% CTNNB1 -mutated tumors were found in the strong or in the weak activation program, most of the AXIN1 -mutated tumors (>70%) were found in the subgroup with no activation. We validated this result by demonstrating that mice with a hepatocyte specific AXIN1 deletion developed HCC in the absence of β-catenin induction. We defined a 329-gene signature common in human and mouse AXIN1 mutated HCC that is highly enriched in Notch and YAP oncogenic signatures. Conclusions AXIN1 -mutated HCCs occur independently of the Wnt/β-catenin pathway and involve Notch and YAP pathways. These pathways constitute potentially interesting targets for the treatment of HCC caused by AXIN1 mutations. Lay summary Liver cancer has a poor prognosis. Defining the molecular pathways involved is important for developing new therapeutic approaches. The Wnt/β-catenin pathway is the most frequently deregulated pathway in hepatocellular carcinoma (HCC). Mutations of AXIN1 , a member of this pathway, represent about 10% of HCC mutations. Using both human HCC collections and engineered mouse models of liver cancers with AXIN1 mutation or deletion, we defined a common signature of liver tumors mutated for AXIN1 and demonstrate that these tumors occur independently of the activation of the Wnt/β-catenin pathway.
- Published
- 2018
32. Letter to the Editor: Comment on Qiao et al
- Author
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Christine Perret and Hélène Gilgenkrantz
- Subjects
Mice ,Letter to the editor ,Hepatology ,Carcinogenesis ,Diagnostic Tests, Routine ,Philosophy ,Animals ,Theology ,beta Catenin ,Sequence Deletion - Published
- 2019
33. La révolution des CRISPR est en marche
- Author
-
Hélène Gilgenkrantz
- Subjects
General Medicine ,Biology ,General Biochemistry, Genetics and Molecular Biology - Published
- 2014
34. Un modèle murin pour une infection chronique méconnue : l’hépatite E !
- Author
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Jérôme Gouttenoire, Hélène Gilgenkrantz, and Vincent Mallet
- Subjects
0301 basic medicine ,Heterografts ,business.industry ,Transgene ,General Medicine ,Hepatitis E ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Chronic infection ,030104 developmental biology ,0302 clinical medicine ,Chronic disease ,Murine model ,Immunology ,medicine ,030211 gastroenterology & hepatology ,business - Published
- 2016
35. Tous les hépatocytes ne sont pas égaux entre eux !
- Author
-
Laurent Dollé, Hélène Gilgenkrantz, Basis (bio)-medische wetenschappen, and Laboratorium Levercelbiologie
- Subjects
General Medicine ,Organ Size ,Biology ,Axin Protein ,Molecular biology ,General Biochemistry, Genetics and Molecular Biology - Published
- 2015
36. HNF4α : un prince charmant pour l’insuffisance hépatique terminale ?
- Author
-
Pascale Bossard and Hélène Gilgenkrantz
- Subjects
business.industry ,Cellular differentiation ,Liver failure ,General Medicine ,Biology ,medicine.disease ,Molecular biology ,General Biochemistry, Genetics and Molecular Biology ,Liver regeneration ,Genetic therapy ,Gene expression profiling ,Text mining ,Hepatocyte nuclear factor 4 ,Fibrosis ,medicine ,business - Published
- 2015
37. Understanding Liver Regeneration: From Mechanisms to Regenerative Medicine
- Author
-
Hélène, Gilgenkrantz and Alexandra, Collin de l'Hortet
- Subjects
Liver Diseases ,Hepatocytes ,Animals ,Humans ,Regenerative Medicine ,Liver Regeneration - Abstract
Liver regeneration is a complex and unique process. When two-thirds of a mouse liver is removed, the remaining liver recovers its initial weight in approximately 10 days. The understanding of the mechanisms responsible for liver regeneration may help patients needing large liver resections or transplantation and may be applied to the field of regenerative medicine. All differentiated hepatocytes are capable of self-renewal, but different subpopulations of hepatocytes seem to have distinct proliferative abilities. In the setting of chronic liver diseases, a ductular reaction ensues in which liver progenitor cells (LPCs) proliferate in the periportal region. Although these LPCs have the capacity to differentiate into hepatocytes and biliary cells in vitro, their ability to participate in liver regeneration is far from clear. Their expansion has even been associated with increased fibrosis and poorer prognosis in chronic liver diseases. Controversies also remain on their origin: lineage studies in experimental mouse models of chronic injury have recently suggested that these LPCs originate from hepatocyte dedifferentiation, whereas in other situations, they seem to come from cholangiocytes. This review summarizes data published in the past 5 years in the liver regeneration field, discusses the mechanisms leading to regeneration disruption in chronic liver disorders, and addresses the potential use of novel approaches for regenerative medicine.
- Published
- 2017
38. [Autophagy in chronic liver diseases: a friend rather than a foe?]
- Author
-
Philippe, Gual, Hélène, Gilgenkrantz, and Sophie, Lotersztajn
- Subjects
Non-alcoholic Fatty Liver Disease ,Liver Diseases ,Chronic Disease ,Autophagy ,Disease Progression ,Animals ,Humans ,Liver Diseases, Alcoholic - Abstract
Within recycling damaged cell components, autophagy maintains cell homeostasis. Thus, it has been anticipated that autophagy would play an essential role in the pathogenesis of chronic liver diseases. Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the most prevalent chronic liver diseases in Western countries, sharing common histopathologic features and a common disease progression. In this review, we discuss the role of autophagy at different stages of NAFLD and ALD as well as in liver regeneration and hepatocarcinogenesis.
- Published
- 2017
39. Effets paradoxaux du cannabis sur la mémoire
- Author
-
Hélène Gilgenkrantz
- Subjects
0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,business.industry ,Medicine ,General Medicine ,business ,General Biochemistry, Genetics and Molecular Biology - Published
- 2018
40. Une seule cellule souche dans le foie : l’hépatocyte !
- Author
-
Hélène Gilgenkrantz
- Subjects
medicine.anatomical_structure ,Liver cytology ,Hepatocyte ,Cancer research ,medicine ,General Medicine ,Stem cell ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Stem cell niche - Published
- 2015
41. [A murine model for an ignored chronic infection: hepatitis E !]
- Author
-
Hélène, Gilgenkrantz, Jérôme, Gouttenoire, and Vincent, Mallet
- Subjects
Disease Models, Animal ,Mice ,Mice, Inbred NOD ,Chronic Disease ,Ribavirin ,Hepatocytes ,Animals ,Heterografts ,Humans ,Mice, Transgenic ,Mice, SCID ,Urokinase-Type Plasminogen Activator ,Hepatitis E - Published
- 2016
42. Autophagy in chronic liver diseases: the two faces of Janus
- Author
-
Philippe Gual, Hélène Gilgenkrantz, and Sophie Lotersztajn
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Alcoholic liver disease ,Cirrhosis ,Physiology ,Biology ,Models, Biological ,End Stage Liver Disease ,03 medical and health sciences ,Nonalcoholic fatty liver disease ,medicine ,Autophagy ,Humans ,Evidence-Based Medicine ,Fatty liver ,Cell Biology ,medicine.disease ,Liver regeneration ,3. Good health ,Fatty Liver ,030104 developmental biology ,Liver ,Cancer research ,Steatohepatitis ,Steatosis - Abstract
Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are the leading causes of cirrhosis and increase the risk of hepatocellular carcinoma and liver-related death. ALD and NAFLD share common pathogenic features extending from isolated steatosis to steatohepatitis and steatofibrosis, which can progress to cirrhosis and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of NAFLD and ALD are complex and still unclear. Important links between the regulation of autophagy (macroautophagy and chaperone-mediated autophagy) and chronic liver diseases have been reported. Autophagy may protect against steatosis and progression to steatohepatitis by limiting hepatocyte injury and reducing M1 polarization, as well as promoting liver regeneration. Its role in fibrosis and hepatocarcinogenesis is more complex. It has pro- and antifibrogenic properties depending on the hepatic cell type concerned, and beneficial and deleterious effects on hepatocarcinogenesis at initiating and late phases, respectively. This review summarizes the latest advances on the role of autophagy in different stages of fatty liver disease progression and describes its divergent and cell-specific effects during chronic liver injury.
- Published
- 2016
43. Combined hepatocellular-cholangiocarcinomas exhibit progenitor features and activation of Wnt and TGFβ signaling pathways
- Author
-
Hélène Gilgenkrantz, Cédric Coulouarn, Sébastien Jacques, Anne Audebourg, Catherine Cavard, Florent Dumont, Christine Perret, Pierre-Alexandre Just, Bruno Clément, Benoit Terris, Laura Rubbia-Brandt, Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Microenvironnement et remodelage, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), 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 de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
- Subjects
MESH: Signal Transduction ,Cancer Research ,Pathology ,MESH : Liver Neoplasms ,Cellular differentiation ,MESH: beta Catenin ,ddc:616.07 ,Cholangiocarcinoma/etiology/pathology ,Cholangiocarcinoma ,0302 clinical medicine ,Transforming Growth Factor beta ,MESH: Liver Neoplasms ,MESH: Carcinoma, Hepatocellular ,Wnt Signaling Pathway ,beta Catenin ,Hepatocyte differentiation ,MESH : Prognosis ,Tissue microarray ,Neoplastic Stem Cells/pathology ,Liver Neoplasms ,MESH : Extracellular Matrix ,MESH: Wnt Signaling Pathway ,Wnt signaling pathway ,Cell Differentiation ,General Medicine ,Prognosis ,Extracellular Matrix ,3. Good health ,Transforming Growth Factor beta/physiology ,030220 oncology & carcinogenesis ,Neoplastic Stem Cells ,[ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,030211 gastroenterology & hepatology ,Wnt Signaling Pathway/physiology ,Stem cell ,MESH: Tissue Array Analysis ,MESH : Cell Differentiation ,Signal Transduction ,MESH : Carcinoma, Hepatocellular ,MESH: Cell Differentiation ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,MESH : Wnt Signaling Pathway ,Beta Catenin/physiology ,MESH: Extracellular Matrix ,Biology ,MESH: Prognosis ,MESH: Gene Expression Profiling ,03 medical and health sciences ,MESH : Neoplastic Stem Cells ,medicine ,Extracellular Matrix/physiology ,Humans ,Progenitor cell ,MESH: Transforming Growth Factor beta ,Progenitor ,MESH : Signal Transduction ,MESH: Humans ,Carcinoma, Hepatocellular/etiology/pathology ,Signal Transduction/physiology ,Gene Expression Profiling ,MESH : Gene Expression Profiling ,MESH : Humans ,Liver Neoplasms/etiology/pathology ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,MESH : Cholangiocarcinoma ,MESH : beta Catenin ,MESH: Cholangiocarcinoma ,MESH: Neoplastic Stem Cells ,Gene expression profiling ,Bile Ducts, Intrahepatic ,MESH : Transforming Growth Factor beta ,Bile Duct Neoplasms ,Tissue Array Analysis ,MESH : Tissue Array Analysis - Abstract
International audience; Intrahepatic malignant tumours include hepatocellular carcinomas (HCC), cholangiocarcinomas (CC) and combined hepatocholangiocarcinomas (cHCC-CC), a group of rare and poorly characterized tumours that exhibit both biliary and hepatocytic differentiation. The aim of the study was to characterize the molecular pathways specifically associated with cHCC-CC pathogenesis. We performed a genome-wide transcriptional analysis of 20 histologically defined cHCC-CC and compared them with a series of typical HCC and of CC. Data were analysed by gene set enrichment and integrative genomics and results were further validated in situ by tissue microarray using an independent series of 152 tumours. We report that cHCC-CC exhibit stem/progenitor features, a down-regulation of the hepatocyte differentiation program and a commitment to the biliary lineage. TGFβ and Wnt/β-catenin were identified as the two major signalling pathways activated in cHCC-CC. A β-catenin signature distinct from that observed in well-differentiated HCC with mutant β-catenin was found in cHCC-CC. This signature was associated with microenvironment remodelling and TGFβ activation. Furthermore, integrative genomics revealed that cHCC-CC share characteristics of poorly differentiated HCC with stem cell traits and poor prognosis. The common traits displayed by CC, cHCC-CC and some HCC suggest that these tumours could originate from stem/progenitor cell(s) and raised the hypothesis of a potential continuum between intrahepatic CC, cHCC-CC and poorly differentiated HCC.
- Published
- 2012
44. EGFR: A Master Piece in G1/S Phase Transition of Liver Regeneration
- Author
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Hélène Gilgenkrantz, Jacques-Emmanuel Guidotti, and Alexandra Collin de l'Hortet
- Subjects
Hepatology ,Potential effect ,Review Article ,Cell cycle ,Biology ,Bioinformatics ,Liver regeneration ,Cell biology ,medicine.anatomical_structure ,Growth factor receptor ,Hepatocyte ,medicine ,lcsh:Diseases of the digestive system. Gastroenterology ,Egfr signaling ,lcsh:RC799-869 - Abstract
Unraveling the molecular clues of liver proliferation has become conceivable thanks to the model of two-third hepatectomy. The synchronicity and the well-scheduled aspect of this process allow scientists to slowly decipher this mystery. During this phenomenon, quiescent hepatocytes of the remnant lobes are able to reenter into the cell cycle initiating the G1-S progression synchronously before completing the cell cycle. The major role played by this step of the cell cycle has been emphasized by loss-of-function studies showing a delay or a lack of coordination in the hepatocytes G1-S progression. Two growth factor receptors, c-Met and EGFR, tightly drive this transition. Due to the level of complexity surrounding EGFR signaling, involving numerous ligands, highly controlled regulations and multiple downstream pathways, we chose to focus on the EGFR pathway for this paper. We will first describe the EGFR pathway in its integrity and then address its essential role in the G1/S phase transition for hepatocyte proliferation. Recently, other levels of control have been discovered to monitor this pathway, which will lead us to discuss regulations of the EGFR pathway and highlight the potential effect of misregulations in pathologies.
- Published
- 2012
45. Functional relevance and pro-fibrogenic properties of mucosal-associated invariant T cells (MAIT) during chronic liver diseases
- Author
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Richard Moreau, Pushpa Hegde, Hélène Gilgenkrantz, Badr Kiaf, Lucie Beaudoin, Amine Toubal, E. Weiss, Jinghong Wan, Morgane Mabire, Pierre-Emmanuel Rautou, Philippe Lettéron, Olivia Picq, A. Gupta, Agnès Lehuen, Gladys Ferrere, Sukriti Sukriti, M. Albuquerque, Sophie Lotersztajn, and Valérie Paradis
- Subjects
Hepatology ,business.industry ,Immunology ,Medicine ,Mucosal associated invariant T cell ,business - Published
- 2018
46. Dual Role of CCR2 in the Constitution and the Resolution of Liver Fibrosis in Mice
- Author
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Laurent Rénia, Stanislas Pol, Claudia Mitchell, Vinciane Bizet, Jean-Pierre Couty, Hélène Gilgenkrantz, Dominique Couton, Marie Anson, Vincent Mallet, and Anne-Marie Crain
- Subjects
Liver Cirrhosis ,medicine.medical_specialty ,Pathology ,CCR2 ,Receptors, CCR2 ,Blotting, Western ,CD11c ,Scars ,Inflammation ,Biology ,Pathology and Forensic Medicine ,Immunoenzyme Techniques ,Mice ,Chemokine receptor ,Fibrosis ,Internal medicine ,Matrix Metalloproteinase 13 ,medicine ,Animals ,RNA, Messenger ,Carbon Tetrachloride ,Mice, Knockout ,Liver injury ,Mice, Inbred BALB C ,CD11b Antigen ,Tissue Inhibitor of Metalloproteinase-1 ,Reverse Transcriptase Polymerase Chain Reaction ,Macrophages ,Flow Cytometry ,medicine.disease ,CD11c Antigen ,Endocrinology ,Liver ,Matrix Metalloproteinase 2 ,medicine.symptom ,Hepatic fibrosis ,Regular Articles - Abstract
Inflammation has been shown to induce the progression of fibrosis in response to liver injury. Among inflammatory cells, macrophages and lymphocytes play major roles in both the constitution and resolution of liver fibrosis. The chemokine receptor CCR2 is involved in the recruitment of monocytes to injury sites, and it is known to be induced during the progression of fibrosis in humans. However, its specific role during this process has not yet been unveiled. We first demonstrated that, compared with wild-type mice, CCR2 knockout animals presented a delay in liver injury after acute CCl(4) injection, accompanied by a reduction in infiltrating macrophage populations. We then induced fibrosis using repeated injections of CCl(4) and observed a significantly lower level of fibrotic scars at the peak of fibrosis in mutant animals compared with control mice. This diminished fibrosis was associated with a reduction in F4/80(+)CD11b(+) and CD11c(+) populations at the sites of injury. Subsequent analysis of the kinetics of the resolution of fibrosis showed that fibrosis rapidly regressed in wild-type, but not in CCR2(-/-) mice. The persistence of hepatic injury in mutant animals was correlated with sustained tissue inhibitor of metalloproteinase-1 mRNA expression levels and a reduction in matrix metalloproteinase-2 and matrix metalloproteinase-13 expression levels. In conclusion, these findings underline the role of the CCR2 signaling pathway in both the constitution and resolution of liver fibrotic scars.
- Published
- 2009
47. Transplanted Hepatocytes Over-expressing FoxM1B Efficiently Repopulate Chronically Injured Mouse Liver Independent of Donor Age
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Dina Kremsdorf, Jacques-Emmanuel Guidotti, Claudia Mitchell, Hélène Gilgenkrantz, Robert H. Costa, Dominique Couton, Serban Morosan, Martine Lambert-Blot, and Nicolas Brezillon
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Male ,Cell division ,Mice, Transgenic ,Mice, SCID ,Biology ,Donor age ,Cell therapy ,Mice ,In vivo ,Drug Discovery ,medicine ,Selective advantage ,Genetics ,Animals ,Transplantation, Homologous ,Transcription factor ,Molecular Biology ,Cell Proliferation ,Pharmacology ,Forkhead Box Protein M1 ,Age Factors ,Forkhead Transcription Factors ,Cell cycle ,medicine.anatomical_structure ,Liver ,Hepatocyte ,Immunology ,Cancer research ,Hepatocytes ,Molecular Medicine ,Female - Abstract
Orthotopic liver transplantation is limited by the shortage of liver donors, leading to elderly patients being enrolled as donors with increasing frequency. Alternative strategies such as cell therapy are therefore needed. Because transplanted hepatocytes do not proliferate into a recipient liver, repopulation strategies have been developed. We have previously published a proof of concept that hepatocytes harboring a survival selective advantage can efficiently repopulate a mouse liver. We develop here an alternative approach by conferring a selective proliferative advantage on transplanted hepatocytes over resident ones. FoxM1B is a transcription factor that, when over-expressed into hepatocytes, accelerates the cell cycle and maintains the hepatocyte in vivo proliferative capacity of aged livers. We now demonstrate that transplanted hepatocytes over-expressing FoxM1B repopulate the liver of mice subjected to continuous injury far more efficiently than control hepatocytes. We show that old hepatocytes that over-express FoxM1B retain their cell division capacity and repopulate liver as well as young ones, in contrast with old non-modified hepatocytes, which lose their proliferative capacity. In conclusion, our results point to the potential use of FoxM1B expression in hepatocyte-based therapy protocols in diseases where host hepatocytes are chronically injured, especially if donor hepatocytes come from old livers.
- Published
- 2007
- Full Text
- View/download PDF
48. SRF IS A NEW PLAYER INVOLVED IN LIVER REGENERATION
- Author
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Jacques-Emmanuel Guidotti, Dominique Daegelen, Hélène Gilgenkrantz, Dominique Couton, Claudia Mitchell, M. Ujue Latasa, Claude L. Charvet, Aurélie Lafanechère, David Tuil, Zhenlin Li, Charvet, Claude, Institut Cochin (UMR_S567 / UMR 8104), 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 Cochin (IC UM3 (UMR 8104 / U1016)), Génétique et Physiopathologie des Tissus Musculaires (GPTM), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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Serum Response Factor ,Time Factors ,genetic structures ,Physiology ,[SDV]Life Sciences [q-bio] ,Cell Cycle Proteins ,Mice ,0302 clinical medicine ,Mice, Knockout ,Mice, Inbred BALB C ,0303 health sciences ,Gastroenterology ,conditional inactivation ,Cell cycle ,musculoskeletal system ,Liver regeneration ,Cell biology ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,Liver ,030220 oncology & carcinogenesis ,Hepatocyte ,embryonic structures ,cardiovascular system ,cell cycle ,Transcriptional Activation ,medicine.medical_specialty ,Biology ,Immediate-Early Proteins ,03 medical and health sciences ,Downregulation and upregulation ,In vivo ,Physiology (medical) ,Internal medicine ,Serum response factor ,hepatocyte ,medicine ,Animals ,Hepatectomy ,RNA, Messenger ,Transcription factor ,Cell Proliferation ,030304 developmental biology ,Hepatology ,Regeneration (biology) ,DNA ,eye diseases ,Liver Regeneration ,Mice, Inbred C57BL ,Endocrinology - Abstract
International audience; Various immediate early genes (IEGs) upregulated during the early process of liver regeneration are transcriptional targets of the serum response factor (SRF). We show here that the expression of SRF is rapidly induced in rodent liver after partial hepatectomy. Because the inactivation of the SRF gene in mice is embryonic lethal, the in vivo role of SRF in liver regeneration after partial hepatectomy was analyzed in mutant mice conditionally deleted for SRF in the liver. We demonstrate that SRF is not an essential factor for liver ontogenesis. However, adult mutant mice show impaired liver regeneration after partial hepatectomy, associated with a blunted upregulation of various SRF target IEGs. In conclusion, our work suggests that SRF is an early response transcription factor that may contribute to the initial phases of liver regeneration through its activation of IEGs.
- Published
- 2007
49. Bile acids and FGF receptors: orchestrators of optimal liver regeneration
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Thierry Tordjmann and Hélène Gilgenkrantz
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medicine.medical_treatment ,Fibroblast growth factor ,Sensitivity and Specificity ,Bile Acids and Salts ,Mice ,medicine ,Animals ,Hepatectomy ,Humans ,STAT3 ,Zebrafish ,Cell Proliferation ,biology ,Liver cell ,Regeneration (biology) ,Growth factor ,Gastroenterology ,Recovery of Function ,biology.organism_classification ,Receptors, Fibroblast Growth Factor ,Liver regeneration ,Cell biology ,Liver Regeneration ,medicine.anatomical_structure ,Biochemistry ,Hepatocyte ,biology.protein ,Hepatocytes ,Biomarkers - Abstract
Because it fosters our dreams of immortality, regeneration has been for centuries a matter of fascination for countless biologists and clinicians. While in mammals regeneration is obviously less spectacular than in hydra, newt or zebrafish, it allows, in any case, repairing intestine, skin or liver. The latter organ is seen as a paradigmatic regeneration model because, as for an amputated fin's zebrafish or newt's forelimb, it is indeed possible to follow the complete restoration of a rodent liver mass after a 2/3 partial hepatectomy (PH) within a few days. The caveat is that most of our knowledge about liver regeneration is based on this specific surgical model. The amazing conclusion is that liver regeneration relies mainly on highly differentiated hepatocytes, which, while actively dividing to restore the missing part, maintain their vital functions.1 Hepatocytes are in a quiescent state (G0) in a normal adult liver. Following 2/3 PH, >95% of these parenchymal cells present in the remnant lobes divide in a rather synchronous manner, for one or two rounds of cell division. Other liver cell types, such as macrophages, cholangiocytes or endothelial cells, will divide afterwards. Schematically, one can distinguish two successive main steps allowing proper regeneration. The first phase requires the secretion of cytokines such as tumour necrosis factor-α and interleukin-6 in the very first minutes after PH, which poise hepatocytes to enter G1 phase and to become receptive to growth factors. The second step involves concomitantly metabolic changes, consisting in particular in a transient accumulation of lipid droplets, and in the activation of two growth factor pathways, epidermal growth factor receptor and c-Met. Both pathways then recruit scaffolding proteins and activate multiple intracellular intertwined networks, such as mitogen-activated protein kinases, signal transducer and activator of transcription 3 (STAT3), …
- Published
- 2014
50. Stratégies de repeuplement du foie
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Claudia Mitchell, Hélène Gilgenkrantz, Axel Kahn, Jacques-Emmanuel Guidotti, and Vincent Olivier
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Gynecology ,medicine.medical_specialty ,business.industry ,Liver failure ,medicine ,Insuficiencia hepatica ,General Medicine ,business ,Liver repopulation - Abstract
RESUME Le foie est doue de capacites regeneratrices apres agression et les hepatocytes sont au cœur de ce processus. Pourtant, la transplantation d’hepatocytes isoles reste relativement inefficace, et rares sont les essais cliniques ayant abouti a un resultat therapeutique objectif. Nous avons apporte la preuve de principe qu’en conferant un avantage selectif de survie a des hepatocytes il etait possible de repeupler un foie murin et que cette approche etait efficace et therapeutique dans un modele de deficit en une enzyme majoritairement synthetisee par le foie. En revanche, s’il est possible d’obtenir des hepatocytes derives de la moelle osseuse apres transplantation medullaire, l’efficacite de cette transdifferenciation est bien en deca de tout espoir therapeutique. Les donnees actuelles concernant la plasticite de cellules souches adultes pour la regeneration hepatique seront abordees.
- Published
- 2005
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