It has been shown that SMAD4 knockout mice impairs TGF-β/SMAD3 signal transduction, subsequently triggers modulation of multifunctional roles of TGF-β1 in fibrogenesis via interacting with SMAD transcription factors, including SMAD7 and SMAD3 to impact their transcriptional activities in renal fibrosis (18). This evidence concerns the gene SMAD4 and renal fibrosis.