In this study, our result showed that conditional knockout of TGF-βRII from TECs attenuated Smad2/3 activation and protected against renal injury caused by cisplatin injection, we further found Smad2 aggravated cisplatin-induced AKI in vivo using Smad2 conditional knockout mice, which was further confirmed in vitro using cisplatin-challenged TECs with Smad2 overexpression (OE) or knockdown (KD). The gene discussed is SMAD2; the disease is acute kidney injury.