Molecular profiling of early stage liver fibrosis in patients with chronic hepatitis C virus infection

摘要: The molecular mechanisms of acute hepatitis C virus (HCV) infection, end-stage (cirrhosis), and hepatocellular carcinoma have been extensively studied, but little is known the changes in liver gene expression during early stages fibrosis associated with chronic HCV that is, transition from normal (NL) uninfected patients to first stage (F1-CH-C). To obtain insight into pathogenesis F1-CH-C, we used real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) study mRNA 240 selected genes tissue comparison NL. 54 (22.5%) was significantly different between F1-CH-C NL; 46 were upregulated 8 downregulated F1-CH-C. most noteworthy mainly affected transcriptional network regulated by interferons (IFNs), including both IFN-alpha/beta-inducible (STAT1, STAT2, ISGF3G/IRF9, IFI27, G1P3, G1P2, OAS2, MX1) IFN-gamma-inducible (CXCL9, CXCL10, CXCL11). Interesting, upregulation (but not genes) independent histological scores (grade fibrosis) characteristics (hepatic levels genotype), specific (as compared B (HBV)). Other dysregulated albeit less markedly than IFN-alpha/beta- genes, involved activation lymphocytes infiltrating (IFNG, TNF, CXCL6, IL6, CCL8, CXCR3, CXCR4, CCR2), cell proliferation (p16/CDKN2A, MKI67, p14/ARF), extracellular matrix remodeling (MMP9, ITGA2), lymphangiogenesis (XLKD1/LYVE), oxidative stress (CYP2E1), cytoskeleton microtubule organization (STMN2/SCG10). Thus, a limited number signaling pathways, particularly interferons, are HCV-induced fibrosis. Some identified here could form basis for new approaches aimed at refining IFN-based therapies infection.