Correlation Between TGF-β1 and c-MET Expression in HCV Genotype 4-Induced Liver Fibrosis

Although direct-acting antiviral agents (DAAs) provide hopes for diminution of hepatitis C virus (HCV)-induced liver fibrosis, understanding the molecular mechanisms of crosstalk between signaling pathways in fibrogenesis has remained challenging. In this study, we hypothesize that the mesenchymal-epithelial transition factor (c-MET) and transforming growth factor-beta 1 (TGF-beta 1) pathways perform antagonistic functions rather than in concert. One hundred eighteen subjects were selected for this study: 14 controls and 104 chronic HCV patients with different grades of fibrosis (42 F0-F1 and 62 F2-F4). c-MET mRNA was measured by quantitative real-time PCR in peripheral blood mononuclear cells. Since both c-MET and TGF-beta 1 are secretory proteins, their serum levels were tested by enzyme-linked immunosorbent assay. Although the mRNA expression level of the c-MET gene correlated neither with HCV infection nor with grades of liver fibrosis, serum levels of c-MET and TGF-beta 1 proteins showed strictly opposite correlation with grades of liver fibrosis. When comparing protein levels in late fibrosis (F2-F4) with levels in early fibrosis (F0-F1), c-MET was significantly decreased (P = 0.001) and TGF-beta 1 was significantly increased (P = 0.001) at progressive stages of fibrosis. Pearson's correlation coefficient (r = -0.23, P = 0.05) between serum levels of c-MET and TGF-beta 1 proteins confirms the negative interaction between both pathways.