SMAD3 and renal fibrosis: In renal fibrosis, interestingly, although Smad2 shares a high degree of structural similarity to Smad3, overexpression of Smad2 attenuated TGF-β1-induced Smad3 phosphorylation and collagen I matrix, indicating that Smad2 works antagonistically to Smad3 in the progression of renal fibrosis [33].