SMAD3 and diabetic kidney disease: Mechanistically, immunohistochemistry and western blot analysis detected that compared to diabetic WT mice, activation of both TGF-β/Smad3 and NF-κB/p65 signaling as evidenced by increased phosphorylation of Smad3 and NF-κB/p65 and their nuclear translocation in the diabetic kidneys was suppressed in the diabetic kidneys of Tg mice (Figure 3), demonstrating that latent TGF-β1 may protect against DKD by suppressing TGF-β/Smad-mediated renal fibrosis and NF-κB/p65-driven renal inflammation.