In the context of DN, TGF-β/Smad3 signaling is highly activated, which is associated with downregulation of renal Smad7, resulting in renal fibrosis as seen in both experimental and human diabetic kidneys [11], [30] and in vitro under high glucose and advanced glycation end products conditions [30], [31]. This evidence concerns the gene SMAD3 and liver dysplastic nodule.