This finding largely extended a previous observation in vitro that ANG II-induced TGF-β/Smad3-mediated renal fibrosis in cultured renal tubular epithelial cells is associated with down-regulation of Smad7 via AT1R-Smurf2-dependent ubiquitin degradation of Smad7 [11]. The gene discussed is SMURF2; the disease is renal fibrosis.