Furthermore, the findings that enhanced TGF-β/Smad3-mediated renal fibrosis and NF-κB-dependent renal inflammation in Smad7 KO mice were associated with up-regulation of Sp1 and down-regulation of miR-29b in the hypertensive kidney also provided new mechanisms for understanding the protective role of Smad7 in ANG II-mediated hypertensive nephropathy. This evidence concerns the gene SMAD7 and renal fibrosis.