Global knockout of Smad3 protects against ischemic AKI by reducing IL-6 production.114 Moreover, Smad3 binds directly to p27 and inhibits the CDK2/cyclin E complex, thereby promoting AKI.115 As an inhibitory Smad, Smad7 protects against AKI by rescuing tubular epithelial cells from Smad3-mediated G1 cell cycle arrest.116 The function of Smad2 in AKI has drawn attention. This evidence concerns the gene SMAD7 and acute kidney injury.