In our studies, upregulation of TGF-β1 receptor and phospho-SMAD2/3 levels, together with enhanced localization of phospho-SMAD3 in the diabetic lung and upregulated ERK and RAGE levels, suggested that diabetes-induced fibrosis was mediated by the activation of both SMAD-dependent and SMAD-independent pathways (Fig. 5). This evidence concerns the gene SMAD2 and diabetes mellitus.