Indeed, fibroblasts from Smad3-/- mice fail to auto-induce TGF-β1 expression [10], and Smad3-/- mice are protected in several models of tissue fibrosis (UUO, diabetic nephropathy and angiotensin II-induced renal and cardiac fibrosis), demonstrating a key role for TGF-β/Smad3 signalling in tissue fibrosis [9], [11]–[14]. This evidence concerns the gene SMAD3 and diabetic kidney disease.