Full metadata record
DC Field | Value | Language |
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dc.creator | Sobrevals, L. (Luciano) | - |
dc.creator | Romero-Trevejo, J.L. (José Lorenzo) | - |
dc.creator | Monreal, I. (Iñaki) | - |
dc.creator | Juanarena, N. (Nerea) | - |
dc.creator | Razquin, N. (Nerea) | - |
dc.creator | González-Aseguinolaza, G. (Gloria) | - |
dc.creator | Fortes, P. (Puri) | - |
dc.creator | Rodriguez-Ortigosa, C.M. (Carlos M.) | - |
dc.creator | Gondi, G. (Gabor) | - |
dc.date.accessioned | 2010-09-17T07:58:58Z | - |
dc.date.available | 2010-09-17T07:58:58Z | - |
dc.date.issued | 2009-10-27 | - |
dc.identifier.citation | Sobrevals 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.issn | 0270-9139 | - |
dc.identifier.uri | https://hdl.handle.net/10171/12605 | - |
dc.description.abstract | Weinvestigated 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.iso | eng | es_ES |
dc.publisher | Wiley-Blackwell | es_ES |
dc.rights | info:eu-repo/semantics/closedAccess | - |
dc.subject | Insulin-Like | es_ES |
dc.subject | Growth | es_ES |
dc.subject | Gene | es_ES |
dc.subject | Transfer to Cirrhotic | es_ES |
dc.subject | Liver | es_ES |
dc.subject | Induces | es_ES |
dc.subject | Fibrolysis | es_ES |
dc.subject | Fibrogenesis | es_ES |
dc.title | Insulin-like growth factor I gene transfer to cirrhotic liver induces fibrolysis and reduces fibrogenesus leading to cirrhosis reversion in rats | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.identifier.doi | http://dx.doi.org/10.1002/hep.23412 | es_ES |
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