As known that TGF-βis usually high expressed in variety of renal disease, including obstructive nephropathy, and TGF-β, as a major mediator of ECM, can induce the fibrosis development in diabetic nephropathy and tubulointerstitial fibrosis by phoshorylating downstream fators Smad2/3 which can induce the expression of ECM proteins such as fibronectin and collagen-I [54,55,56]. This evidence concerns the gene SMAD2 and diabetic kidney disease.