SMAD3 and renal fibrosis: Of note, Smad3 promotes renal fibrosis by directly binding to the promoter region of collagens to trigger their production (Vindevoghel et al., 1998; Chen et al., 1999), and inhibiting the ECM degradation via induction of TIMP-1 while reducing MMP-1 activities in fibroblasts (Yuan and Varga, 2001).