SMAD3 and renal fibrosis: In addition, as ERK1/2 can interact with Smad3 to TGF-β1-stimulated multiple biological functions including renal fibrosis (Nakagawa et al., 2005), I-BET151 may also inhibit renal fibrosis through interfering with ERK1/2-mediated regulation of Smad3 and other profibrotic machinery downstream of TGFβ receptors.