SMAD2 and renal fibrosis: Similarly, in the case of renal fibrosis, HQD could ameliorate the ipsilateral kidney fibrosis in a dose-dependent manner by downregulation of TGF-β1, TGF-β receptor I and II, Smad2, P-Smad2, Smad4, α-SMA, and collagen I, III, and IV expression.