20 results on '"Gilgenkrantz, H."'
Search Results
2. [The liver remains a young organ even in old age !]
- Author
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Gilgenkrantz H
- Subjects
- Humans, Liver
- Published
- 2022
- Full Text
- View/download PDF
3. The aged liver: Beyond cellular senescence.
- Author
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Allaire M and Gilgenkrantz H
- Subjects
- Aged, Homeostasis, Humans, Liver physiology, Liver Diseases etiology, Aging pathology, Cellular Senescence, Liver pathology
- Abstract
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., (Copyright © 2019. Published by Elsevier Masson SAS.)
- Published
- 2020
- Full Text
- View/download PDF
4. The impact of steatosis on liver regeneration.
- Author
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Allaire M and Gilgenkrantz H
- Subjects
- Animals, Humans, Liver drug effects, Liver metabolism, Signal Transduction, Fatty Liver physiopathology, Liver pathology, Liver Regeneration
- 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
- Full Text
- View/download PDF
5. Autophagy in chronic liver diseases: the two faces of Janus.
- Author
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Gual P, Gilgenkrantz H, and Lotersztajn S
- Subjects
- Evidence-Based Medicine, Humans, Liver pathology, Models, Biological, Autophagy, End Stage Liver Disease pathology, End Stage Liver Disease physiopathology, Fatty Liver pathology, Fatty Liver physiopathology, Liver physiopathology
- 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., (Copyright © 2017 the American Physiological Society.)
- Published
- 2017
- Full Text
- View/download PDF
6. [Axin-2+ hepatocytes are better at maintaining liver mass].
- Author
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Dollé L and Gilgenkrantz H
- Subjects
- Animals, Humans, Organ Size, Axin Protein physiology, Hepatocytes physiology, Liver cytology, Liver growth & development
- Published
- 2015
- Full Text
- View/download PDF
7. [The hepatocyte is the only stem cell in the liver].
- Author
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Gilgenkrantz H
- Subjects
- Animals, Hepatocytes cytology, Humans, Liver Regeneration physiology, Mice, Rats, Stem Cell Niche, Hepatocytes physiology, Liver cytology, Stem Cells cytology, Stem Cells physiology
- Published
- 2015
- Full Text
- View/download PDF
8. GH receptor plays a major role in liver regeneration through the control of EGFR and ERK1/2 activation.
- Author
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Zerrad-Saadi A, Lambert-Blot M, Mitchell C, Bretes H, Collin de l'Hortet A, Baud V, Chereau F, Sotiropoulos A, Kopchick JJ, Liao L, Xu J, Gilgenkrantz H, and Guidotti JE
- Subjects
- Animals, Crosses, Genetic, Enzyme Activation, Enzyme Induction, ErbB Receptors genetics, G1 Phase, Insulin-Like Growth Factor I genetics, Insulin-Like Growth Factor I metabolism, Liver cytology, Male, Mice, Mice, Knockout, Mice, Transgenic, Phosphorylation, Protein Processing, Post-Translational, RNA, Messenger metabolism, Receptors, Somatotropin genetics, ErbB Receptors metabolism, Liver physiology, Liver Regeneration, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 metabolism, Receptors, Somatotropin physiology, Signal Transduction
- Abstract
GH is a pleiotropic hormone that plays a major role in proliferation, differentiation, and metabolism via its specific receptor. It has been previously suggested that GH signaling pathways are required for normal liver regeneration but the molecular mechanisms involved have yet to be determined. The aim of this study was to identify the mechanisms by which GH controls liver regeneration. We performed two thirds partial hepatectomies in GH receptor (GHR)-deficient mice and wild-type littermates and showed a blunted progression in the G(1)/S transition phase of the mutant hepatocytes. This impaired liver regeneration was not corrected by reestablishing IGF-1 expression. Although the initial response to partial hepatectomy at the priming phase appeared to be similar between mutant and wild-type mice, cell cycle progression was significantly blunted in mutant mice. The main defect in GHR-deficient mice was the deficiency of the epidermal growth factor receptor activation during the process of liver regeneration. Finally, among the pathways activated downstream of GHR during G(1) phase progression, namely Erk1/2, Akt, and signal transducer and activator of transcription 3, we only found a reduced Erk1/2 phosphorylation in mutant mice. In conclusion, our results demonstrate that GH signaling plays a major role in liver regeneration and strongly suggest that it acts through the activation of both epidermal growth factor receptor and Erk1/2 pathways.
- Published
- 2011
- Full Text
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9. [Hippo-YAP signaling pathway in the liver: more than a size gatekeeper!].
- Author
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Gilgenkrantz H
- Subjects
- Animals, Animals, Genetically Modified, Cell Cycle Proteins, Drosophila melanogaster genetics, Hepatocyte Growth Factor physiology, Homeostasis, Intercellular Signaling Peptides and Proteins physiology, Liver Neoplasms, Experimental genetics, Liver Neoplasms, Experimental metabolism, Liver Neoplasms, Experimental pathology, Mammals genetics, Mice, Models, Biological, Phosphorylation, Protein Processing, Post-Translational, Proto-Oncogene Proteins physiology, Species Specificity, YAP-Signaling Proteins, Drosophila Proteins physiology, Drosophila melanogaster growth & development, Intracellular Signaling Peptides and Proteins physiology, Liver physiology, Mammals growth & development, Nuclear Proteins physiology, Organ Size physiology, Protein Serine-Threonine Kinases physiology, Signal Transduction physiology, Trans-Activators physiology, Transcription Factors physiology
- Published
- 2011
- Full Text
- View/download PDF
10. Transient micro-elastography: A novel non-invasive approach to measure liver stiffness in mice.
- Author
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Bastard C, Bosisio MR, Chabert M, Kalopissis AD, Mahrouf-Yorgov M, Gilgenkrantz H, Mueller S, and Sandrin L
- Subjects
- Amyloidosis chemically induced, Amyloidosis pathology, Animals, Carbon Tetrachloride toxicity, Female, Liver drug effects, Male, Mice, Mice, Inbred Strains, Elasticity Imaging Techniques methods, Liver pathology
- Abstract
Aim: To develop and validate a transient micro-elastography device to measure liver stiffness (LS) in mice., Methods: A novel transient micro-elastography (TME) device, dedicated to LS measurements in mice with a range of measurement from 1-170 kPa, was developed using an optimized vibration frequency of 300 Hz and a 2 mm piston. The novel probe was validated in a classical fibrosis model (CCl(4)) and in a transgenic murine model of systemic amyloidosis., Results: TME could be successfully performed in control mice below the xiphoid cartilage, with a mean LS of 4.4 ± 1.3 kPa, a mean success rate of 88%, and an excellent intra-observer agreement (0.98). Treatment with CCl(4) over seven weeks drastically increased LS as compared to controls (18.2 ± 3.7 kPa vs 3.6 ± 1.2 kPa). Moreover, fibrosis stage was highly correlated with LS (Spearman coefficient = 0.88, P < 0.01). In the amyloidosis model, much higher LS values were obtained, reaching maximum values of > 150 kPa. LS significantly correlated with the amyloidosis index (0.93, P < 0.0001) and the plasma concentration of mutant hapoA-II (0.62, P < 0.005)., Conclusion: Here, we have established the first non-invasive approach to measure LS in mice, and have successfully validated it in two murine models of high LS.
- Published
- 2011
- Full Text
- View/download PDF
11. [Decline of liver'age-dependent regenerative capacities: some molecular tracks].
- Author
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Gilgenkrantz H and Guidotti JE
- Subjects
- CCAAT-Enhancer-Binding Protein-alpha physiology, Humans, Models, Biological, Aging physiology, Liver growth & development, Liver physiology, Liver Regeneration physiology
- Published
- 2007
- Full Text
- View/download PDF
12. Transplanted hepatocytes over-expressing FoxM1B efficiently repopulate chronically injured mouse liver independent of donor age.
- Author
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Brezillon N, Lambert-Blot M, Morosan S, Couton D, Mitchell C, Kremsdorf D, Costa RH, Gilgenkrantz H, and Guidotti JE
- Subjects
- Age Factors, Animals, Cell Proliferation, Female, Forkhead Box Protein M1, Forkhead Transcription Factors physiology, Hepatocytes cytology, Liver injuries, Liver metabolism, Male, Mice, Mice, SCID, Mice, Transgenic, Transplantation, Homologous methods, Forkhead Transcription Factors genetics, Hepatocytes metabolism, Hepatocytes transplantation, Liver surgery
- 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
13. Delayed liver regeneration in mice lacking liver serum response factor.
- Author
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Latasa MU, Couton D, Charvet C, Lafanechère A, Guidotti JE, Li Z, Tuil D, Daegelen D, Mitchell C, and Gilgenkrantz H
- Subjects
- Animals, Cell Cycle, Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, Cell Proliferation, DNA biosynthesis, Hepatectomy, Immediate-Early Proteins genetics, Immediate-Early Proteins metabolism, Liver cytology, Liver physiology, Liver surgery, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, RNA, Messenger metabolism, Serum Response Factor deficiency, Serum Response Factor genetics, Time Factors, Transcriptional Activation, Liver metabolism, Liver Regeneration genetics, Serum Response Factor metabolism
- Abstract
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
- Full Text
- View/download PDF
14. Mobilizing stem cells to repair liver after surgery: dream or reality?
- Author
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Mallet VO and Gilgenkrantz H
- Subjects
- AC133 Antigen, Animals, Antigens, CD genetics, Antigens, CD metabolism, Glycoproteins genetics, Glycoproteins metabolism, Hepatectomy, Humans, Mice, Mice, Knockout, Peptides genetics, Peptides metabolism, Stem Cells cytology, Liver cytology, Liver pathology, Liver physiology, Liver surgery, Liver Regeneration, Stem Cells physiology
- Published
- 2005
- Full Text
- View/download PDF
15. [Hepatic stem cells: it's quite an undertaking!].
- Author
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Gilgenkrantz H
- Subjects
- Animals, Humans, Mesenchymal Stem Cells, Liver cytology, Stem Cells physiology
- Published
- 2004
- Full Text
- View/download PDF
16. The combination of ischemic preconditioning and liver Bcl-2 overexpression is a suitable strategy to prevent liver and lung damage after hepatic ischemia-reperfusion.
- Author
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Peralta C, Perales JC, Bartrons R, Mitchell C, Gilgenkrantz H, Xaus C, Prats N, Fernández L, Gelpí E, Panés J, and Roselló-Catafau J
- Subjects
- Animals, Mice, Mice, Inbred CBA, Mice, Transgenic, Proto-Oncogene Proteins c-bcl-2 genetics, Ischemic Preconditioning, Liver pathology, Liver Circulation, Lung pathology, Proto-Oncogene Proteins c-bcl-2 biosynthesis, Pulmonary Circulation, Reperfusion Injury metabolism
- Abstract
The present study evaluates the effectiveness of ischemic preconditioning and Bcl-2 overexpression against the liver and lung damage that follow hepatic ischemia-reperfusion and investigates the underlying protective mechanisms. Preconditioning and Bcl-2, respectively, reduced the increased tumor necrosis factor (TNF) and macrophage inflammatory protein-2 (MIP)-2 levels observed after hepatic reperfusion. Bcl-2 overexpression or anti-MIP-2 pretreatment seems to be more effective than preconditioning or anti-TNF pretreatment against inflammatory response, microcirculatory disorders, and subsequent hepatic ischemia-reperfusion injury. Furthermore, each one of these strategies individually was unable to completely inhibit hepatic injury. The combination of preconditioning and Bcl-2 overexpression as well as the combined anti-TNF and anti-MIP-2 pretreatment totally prevented hepatic injury, whereas the benefits of preconditioning and Bcl-2 were abolished by TNF and MIP-2. In contrast to preconditioning, Bcl-2 did not modify lung damage induced by hepatic reperfusion. This could be explained by the differential effect of both treatments on TNF release. Anti-TNF therapy or preconditioning, by reducing TNF release, reduced pulmonary inflammatory response, whereas the benefits of preconditioning on lung damage were abolished by TNF. Thus, the induction of both Bcl-2 overexpression in liver and preconditioning, as well as pharmacological strategies that simulated their benefits, such as anti-TNF and anti-MIP-2 therapies, could be new strategies aimed to reduce lung damage and inhibit the hepatic injury associated with hepatic ischemia-reperfusion.
- Published
- 2002
- Full Text
- View/download PDF
17. [Liver repopulation: the selective advantage concept].
- Author
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Mallet VO, Regimbeau JM, Mitchell C, Guidotti JE, Soubrane O, and Gilgenkrantz H
- Subjects
- Animals, Bone Marrow Cells, Gene Transfer Techniques, Genetic Therapy, Genetic Vectors, Hepatocytes, Humans, Liver Diseases therapy, Liver Regeneration, Liver cytology
- Published
- 2002
18. Liver repopulation by Bcl-x(L) transgenic hepatocytes.
- Author
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Mitchell C, Mallet VO, Guidotti JE, Goulenok C, Kahn A, and Gilgenkrantz H
- Subjects
- Animals, Animals, Genetically Modified genetics, Antibodies pharmacology, Apoptosis physiology, Liver drug effects, Mice, Mice, Inbred CBA, Mice, Inbred Strains, Proto-Oncogene Proteins c-bcl-2 genetics, bcl-X Protein, fas Receptor immunology, fas Receptor physiology, Hepatocytes cytology, Hepatocytes physiology, Liver cytology, Liver physiology, Liver Regeneration physiology, Proto-Oncogene Proteins c-bcl-2 metabolism
- Abstract
Liver repopulation could constitute a potential therapeutic alternative to liver transplantation in the future. Therefore, the development of liver repopulation strategies is of major interest. We have previously reported that Bcl-2-expressing hepatocytes are resistant to Fas-mediated apoptosis and that these hepatocytes, when transplanted into the spleen, are able to repopulate the liver of normal mice submitted to Fas-mediated apoptosis. We now show that Bcl-x(L)-overexpressing hepatocytes are able to repopulate up to 10% of a normal mouse liver treated with successive injections of anti-Fas antibody. We show that a twofold overexpression of Bcl-x(L) is sufficient to confer a selective advantage to hepatocytes submitted to anti-Fas antibody. Moreover, repopulation percentages obtained here were comparable to those obtained when Bcl-2 hepatocytes were transplanted, suggesting that both proteins are equivalent in conferring a selective advantage to hepatocytes submitted to anti-Fas antibody.
- Published
- 2002
- Full Text
- View/download PDF
19. Therapeutic liver repopulation in a mouse model of hypercholesterolemia.
- Author
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Mitchell C, Mignon A, Guidotti JE, Besnard S, Fabre M, Duverger N, Parlier D, Tedgui A, Kahn A, and Gilgenkrantz H
- Subjects
- Animals, Apolipoproteins E blood, Apolipoproteins E genetics, Apolipoproteins E metabolism, Arteriosclerosis pathology, Cholesterol blood, Disease Models, Animal, Humans, Lipoproteins blood, Liver metabolism, Liver pathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Mutation, Proto-Oncogene Proteins c-bcl-2 metabolism, Cell Transplantation, Hypercholesterolemia therapy, Liver cytology
- Abstract
Liver repopulation constitutes an attractive approach for the treatment of liver disorders or of diseases requiring abundant secretion of an active protein. We have described previously a model of selective repopulation of a normal liver by Fas/CD95-resistant hepatocytes, in which we achieved up to 16% hepatocyte repopulation. In the present study, we investigated the therapeutic efficacy of this strategy. With this aim, apolipoprotein E (ApoE) knockout mice were transplanted with Fas/CD95-resistant hepatocytes which constitutively express ApoE. Transplanted mice were submitted to weekly injections of non-lethal doses of the Fas agonist antibody Jo2. After 8 weeks of treatment, we obtained up to 30% of the normal level of plasma ApoE. ApoE secretion was accompanied by a drastic and significant decrease in total plasma cholesterol, which even fell to normal levels. Moreover, this secretion was sufficient to markedly reduce the progression of atherosclerosis. These results demonstrate the efficacy of this repopulation approach for correcting a deficiency in a protein secreted by the liver.
- Published
- 2000
- Full Text
- View/download PDF
20. Selective repopulation of normal mouse liver by Fas/CD95-resistant hepatocytes.
- Author
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Mignon A, Guidotti JE, Mitchell C, Fabre M, Wernet A, De La Coste A, Soubrane O, Gilgenkrantz H, and Kahn A
- Subjects
- Animals, Chimera, Female, Genes, bcl-2, Humans, Male, Mice, Mice, Inbred CBA, Mice, Transgenic, Apoptosis, Cell Transplantation methods, Liver cytology, Selection, Genetic, fas Receptor metabolism
- Abstract
Hepatocyte transplantation might represent a potential therapeutic alternative to liver transplantation in the future; however, transplanted cells have a limited capacity to repopulate the liver, as they do not proliferate under normal conditions. Recently, studies in urokinase (uPA) transgenic mice and in fumarylacetoacetate hydrolase (FAH)-deficient mice have shown that the liver can be repopulated by genetically engineered hepatocytes harboring a selective advantage over resident hepatocytes. We have reported that transgenic mice expressing human Bcl-2 in their hepatocytes are protected from Fas/CD95-mediated liver apoptosis. We now show that Bcl-2 transplanted hepatocytes selectively repopulate the liver of mice treated with nonlethal doses of the anti-Fas antibody Jo2. FK 506 immunosuppressed mice were transplanted by splenic injection with Bcl-2 hepatocytes. The livers of female recipients were repopulated by male Bcl-2 transgenic hepatocytes, as much as 16%, after 8 to 12 administrations of Jo2. This only occurred after anti-Fas treatment, confirming that resistance to Fas-induced apoptosis constituted the selective advantage of these transplanted hepatocytes. Thus, we have demonstrated a method for increasing genetic reconstitution of the liver through selective repopulation with modified transgenic hepatocytes, which will allow optimization of cell and gene therapy in the liver.
- Published
- 1998
- Full Text
- View/download PDF
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