SMAD3 and Hepatic fibrosis: However, after HSC transdifferentiation to MFB, the ability of TGF-β1 to induce Smad7 expression decreases, Smad2 and Smad3 are phosphorylated, the TGF-β1/Smads signaling pathway is activated, and ECM is secreted in large amounts, accelerating liver fibrosis [39–41].