Viral Hepatitis
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jun 28, 2006; 12(24): 3821-3828
Published online Jun 28, 2006. doi: 10.3748/wjg.v12.i24.3821
Increased hepatic expression of insulin-like growth factor-I receptor in chronic hepatitis C
José Tadeu Stefano, Maria Lúcia Corrêa-Giannella, Cristiane Maria Freitas Ribeiro, Venâncio Avancini Ferreira Alves, Paulo Celso Bosco Massarollo, Marcel Cerqueira Cesar Machado, Daniel Giannella-Neto
José Tadeu Stefano, Laboratory for Cellular and Molecular Endocrinology, University of Sao Paulo Medical School, Brazil
Maria Lúcia Corrêa-Giannella, Daniel Giannella-Neto, Laboratory for Cellular and Molecular Endocrinology, University of Sao Paulo Medical School, Diabetes Unit, Division of Endocrinology, Brazil
Cristiane Maria Freitas Ribeiro, Department of Pathology, Santa Casa de Misericórdia de Sao Paulo, Brazil
Venâncio Avancini Ferreira Alves, Department of Pathology, University of Sao Paulo Medical School, Brazil
Paulo Celso Bosco Massarollo, Marcel Cerqueira Cesar Machado, Laboratory for Experimental Surgery, University of Sao Paulo Medical School, Brazil
Co-first-author: José Tadeu Stefano and Maria Lúcia Corrêa-Giannella
Co-Correspondence: José Tadeu Stefano
Correspondence to: Professor Dr. Daniel Giannella-Neto, Laboratory for Cellular and Molecular Endocrinology, University of Sao Paulo Medical School, Diabetes Unit, Division of Endocrinology, Av. Dr. Arnaldo, 455-Exclude #4307, 01246-903- Sao Paulo, Brazil. dag@usp.br
Telephone: +55-11-30667467 Fax: +55-11-30667050
Received: September 16, 2005
Revised: October 16, 2005
Accepted: October 26, 2005
Published online: June 28, 2006
Abstract

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 mRNA expression in liver from patient with CHC.

METHODS: IGF-IR and IGF-I mRNA content were determined by semi-quantitative RT-PCR and IGF-IR protein expression was determined by immunohisto-chemistry 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 mRNA 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 immunohistochemical results showed that the raise in IGF-IR mRNA content was related both to ductular reaction and to increased IGF-IR expression in hepatocytes. A decrease in IGF-IR mRNA 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.

Keywords: Chronic hepatitis C; Insulin-like growth factor I; Insulin-like growth factor I receptor; Ductular reaction; Hepatocyte regeneration; Ischemia-reperfusion