Hepatitis C virus proteins do not directly trigger fibrogenic events in cultured human liver myofibroblasts.
Although liver fibrosis is the major complication of hepatitis C virus (HCV) infection, the mechanisms of fibrogenesis in this setting are not completely understood. The aim of this study was to test the direct effect of HCV proteins on signalling- and fibrosis-related events in cultured human liver myofibroblasts, the effector cells of liver fibrogenesis. Cultured myofibroblasts were exposed to recombinant HCV core, a structural protein, and nonstructural proteins (NS) 3, NS 4 and NS 5. HCV proteins did not significantly increase DNA synthesis in myofibroblasts. We then examined if these proteins affected early signalling events. None of the HCV proteins affected the phosphorylation of the mitogen activated protein kinases/extracellular regulated kinases 1 and 2, or of the phosphatidylinositol 3-kinase target, Akt. HCV proteins had also no effect on intracellular calcium concentration. In other experiments, fibrogenesis-related parameters were measured. None of the HCV proteins had any effect on the secretion of type I collagen, tissue inhibitor of matrix metalloproteinases type 1, gelatinase or urokinase. Alpha-smooth muscle actin expression was also not modified. In summary, our experiments do not support a direct effect of these HCV proteins on fibrogenic cells.
Tan
K
K
Groupe de Recherches pour l'Etude du Foie, INSERM E 0362 and IFR 66, Université Victor Segalen Bordeaux 2, Bordeaux, France.
Guibert
C
C
Neaud
V
V
Rosenbaum
J
J
D000199:Actins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism*; D018093:Gelatinases / Q000378:metabolism; D016174:Hepacivirus / Q000737:chemistry* / Q000472:pathogenicity*; D006801:Humans; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
D000199:Actins; D024042:Collagen Type I; D019715:Tissue Inhibitor of Metalloproteinase-1; D014764:Viral Proteins; D004247:DNA; D011494:Protein Kinases; D014568:Urokinase-Type Plasminogen Activator; D018093:Gelatinases; D002118:Calcium