Figure 4.

The interactions between TGF-β1 and ECM/integrin-mediated signaling in hepatocytes in the fibrotic liver. Initially, TGF-β1 inhibits the growth of hepatocytes by inducing the expression of pro-apoptotic molecules, such as PDCD4, via the formation of pSmadC. TGF-β1 stimulates the production of fibrous ECM from activated HSCs/myofibroblasts. The accumulated ECM proteins in turn activate integrins, then these activated integrins and co-existing growth factors inhibit the TGF-β1-induced growth-suppressive signals via the formation of pSmadL, leading to the resistance of hepatocytes to apoptosis, and the promotion of hepatocarcinogenesis.