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


CONCLUSIONS
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.
Stefano
Jose Tadeu
JT
Laboratory for Cellular and Molecular Endocrinology, University of Sao Paulo Medical School, Diabetes Unit, Division of Endocrinology, Brazil.
Correa-Giannella
Maria Lucia
ML
Ribeiro
Cristiane Maria Freitas
CM
Alves
Venancio Avancini Ferreira
VA
Massarollo
Paulo Celso Bosco
PC
Machado
Marcel Cerqueira Cesar
MC
Giannella-Neto
Daniel
D
D000998:Antiviral Agents / Q000627:therapeutic use; D020869:Gene Expression Profiling; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D016898:Interferon-alpha / Q000627:therapeutic use; D008115:Liver Regeneration / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012254:Ribavirin / Q000627:therapeutic use; D015854:Up-Regulation
D000998:Antiviral Agents; D016898:Interferon-alpha; D012333:RNA, Messenger; D012254:Ribavirin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1