SMAD3 and renal fibrosis: In contrast, miR-29 is protective in renal fibrosis and is negatively regulated by TGF-β via Smad3 as the promoter region of miR-29 contains at least two conserved Smad3 binding-sites and Smad3 could physically interact with the promoter region of miR-29 89.Thus, Smad3 acts as a suppressor to negatively regulate miR-29 expression during TGF-β-mediated fibrosis, and deletion of Smad3 enhances miR-29b expression, thereby inhibiting collagen matrix expression under high TGF-β1 and diabetic conditions 89, 96, 97.