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Increased hepatic expression of insulin-like growth factor-Ⅰreceptor in chronic hepatitis C

World Journal of Gastroenterology 2006年第24期12卷 3821-3828页

作者： José Tadeu Stefano Maria Lúcia Corr(e|^)a-Giannella Cristiane Maria Freitas Ribeiro Ven(a|^)ncio Avancini Ferreira Alves Paulo Celso Bosco Massarollo Marcel Cerqueira Cesar Machado Daniel Giannella-Neto Laboratory for Cellular and Molecular Endocrinology University of Sao Paulo Medical School Brazil Laboratory for Cellular and Molecular Endocrinology University of Sao Paulo Medical School Diabetes UnitDivision of EndocrinologyBrazil Department of Pathology Santa Casa de Misericórdia de Sao Paulo Brazil Department of Pathology University of Sao Paulo Medical School Brazil Laboratory for Experimental Surgery University of Sao Paulo Medical School Brazil

AIM： Although increased insulin-like growth factor-I receptor （IGF-IR） gene expression has been reported in hepatocellular carcinoma, studies assessing IGF-IR in chronic hepatitis C （CHC） and cirrhosis are scarce. We therefore aimed to evaluate IGF-IR and IGF-I rnRNA expression in liver from patient with CHC. METHODS： IGF-IR and IGF-I rnRNA content were determined by semi-quantitative RT-PCR and IGF-IR protein expression was determined by immunohistochemistry in hepatic tissue obtained from patients with CHC before （34 patients） and after （10 patients） therapy with interferon-α and ribavirin. RESULTS： An increase of IGF-IR rnRNA content was observed in hepatic tissue obtained from all CHC patients as well as from 6 cadaveric liver donors following orthopic transplantation （an attempt to evaluate normal livers） in comparison to normal liver, while no relevant modifications were detected in IGF-I mRNA content. The irnrnunohistochemical results showed that the raise in IGF-IR rnRNA content was related both to ductular reaction and to increased IGF-IR expression in hepatocytes. A decrease in IGF-IR rnRNA content was observed in patients who achieved sustained virological response after therapy, suggesting an improvement in hepatic damage. CONCLUSION： The up-regulation of IGF-IR expression in hepatocytes of patients with CHC could constitute an attempt to stimulate hepatocyte regeneration. Considering that liver is the organ with the highest levels of IGF-I, our finding of increased IGF-IR expression after both acute and chronic hepatic damage highlights the need for additional studies to elucidate the role of IGF-I in liver regeneration.

关键词： Chronic hepatitis C insulin-like growth factori insulin-like growth factor I receptor Ductular reaction Hepatocyte regeneration Ischemia-reperfusion

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