Once Smad7 is lost, Ang II-induced activation of Smad3 via both TGF-β-dependent and independent pathways is enhanced [7], [8], which results in enhanced Smad3-mediated fibrosis as previously reported in vitro and in a number of mouse models induced by Ang II [8], [11], [12], [14], [15], postmyocardiac infarction [13], obstructive and diabetic nephropathy [18], [31]. This evidence concerns the gene TGFB1 and diabetic kidney disease.