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dc.creatorSobrevals, L. (Luciano)-
dc.creatorRomero-Trevejo, J.L. (José Lorenzo)-
dc.creatorMonreal, I. (Iñaki)-
dc.creatorJuanarena, N. (Nerea)-
dc.creatorRazquin, N. (Nerea)-
dc.creatorGonzález-Aseguinolaza, G. (Gloria)-
dc.creatorFortes, P. (Puri)-
dc.creatorRodriguez-Ortigosa, C.M. (Carlos M.)-
dc.creatorGondi, G. (Gabor)-
dc.date.accessioned2010-09-17T07:58:58Z-
dc.date.available2010-09-17T07:58:58Z-
dc.date.issued2009-10-27-
dc.identifier.citationSobrevals L, Rodriguez C, Romero-Trevejo JL, Gondi G, Monreal I, Paneda A, et al. Insulin-like growth factor I gene transfer to cirrhotic liver induces fibrolysis and reduces fibrogenesis leading to cirrhosis reversion in rats. Hepatology 2010 Mar;51(3):912-921.es_ES
dc.identifier.issn0270-9139-
dc.identifier.urihttps://hdl.handle.net/10171/12605-
dc.description.abstractWeinvestigated whether gene transfer of insulin-like growth factor I (IGF-I) to the hepatic tissue was able to improve liver histology and function in established liver cirrhosis. Rats with liver cirrhosis induced by carbon tetrachloride (CCl4) given orally for 8 weeks were injected through the hepatic artery with saline or with Simian virus 40 vectors encoding IGF-I (SVIGF-I), or luciferase (SVLuc). Animalsweresacrificed8weeksafter vector injection. In cirrhotic ratsweobserved that, whereas IGF-I was synthesized by hepatocytes, IGF-I receptor was predominantly expressed by nonparenchymal cells, mainly in fibrous septa surrounding hepatic nodules. Rats treated with SVIGF-I showed increased hepatic levels of IGF-I, improved liver function tests, and reduced fibrosis in association with diminished -smoothmuscle actin expression, up-regulation of matrix metalloproteases(MMPs)and decreased expression of the tissue inhibitors of MMPs TIM-1 and TIM-2. SVIGF-I therapy induced down-regulation of the profibrogenic molecules transforming growth factor beta (TGF ), amphiregulin, platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF), and vascular endotheliumgrowthfactor(VEGF)andinduction of the antifibrogenicandcytoprotective hepatocyte growth factor (HGF). Furthermore, SVIGF-I-treated animals showed decreased expression of Wilms tumor-1 (WT-1; a nuclear factor involved in hepatocyte dedifferentiation) and up-regulation of hepatocyte nuclear factor 4 alpha (HNF4 ) (which stimulates hepatocellular differentiation). The therapeutic potential of SVIGF-I was also tested in rats with thioacetamide-induced liver cirrhosis. Also in this model, SVIGF-I improved liver function and reduced liver fibrosis in association with up-regulation of HGF and MMPs and down-regulation of tissue inhibitor of metalloproteinase 1 (TIMP-1). Conclusion: IGF-I gene transfer to cirrhotic livers induces MMPs and hepatoprotective factors leading to reversion of fibrosis and improvement of liver function. IGF-I gene therapy may be a useful alternative therapy for patients with advanced cirrhosis without timely access to liver transplantation.es_ES
dc.language.isoenges_ES
dc.publisherWiley-Blackwelles_ES
dc.rightsinfo:eu-repo/semantics/closedAccess-
dc.subjectInsulin-Likees_ES
dc.subjectGrowthes_ES
dc.subjectGenees_ES
dc.subjectTransfer to Cirrhotices_ES
dc.subjectLiveres_ES
dc.subjectInduceses_ES
dc.subjectFibrolysises_ES
dc.subjectFibrogenesises_ES
dc.titleInsulin-like growth factor I gene transfer to cirrhotic liver induces fibrolysis and reduces fibrogenesus leading to cirrhosis reversion in ratses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.identifier.doihttp://dx.doi.org/10.1002/hep.23412es_ES

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