In the UUO and I/R models, SIRT1 activation improved renal fibrosis in proximal tubular cells by deacetylating SMAD3 and SMAD4 and blocking the effect of TGF-β signaling on matrix metalloproteinase-7 (MMP-7), which normally cleaves E-cadherin [25,137,138]. The gene discussed is SMAD4; the disease is renal fibrosis.