Tangshen Formula Improves Diabetes-Associated Myocardial Fibrosis by Inhibiting TGF-β/Smads and Wnt/β-Catenin Pathways

Abstract

Cardiovascular disease has become the main cause of death among complications of diabetes. Myocardial fibrosis is a crucial pathological change of cardiovascular disease. Tangshen Formula (TSF) shows a good clinical effect in the treatment of diabetic kidney disease (DKD). However, whether TSF alleviates diabetes-associated myocardial fibrosis is still unknown. In the present research, we studied the effect and mechanism of TSF in the treatment of myocardial fibrosis in vivo and in vitro . We found that TSF treatment significantly downregulates myocardial fibrosis-related markers, including collagens I and III, and α-SMA. TSF also protects primary mouse cardiac fibroblast (CF) from transforming growth factor-β1- (TGF-β1-) induced damage. Moreover, TSF decreased the expression levels of TGF-β/Smad-related genes (α-SMA, collagens I and III, TGF-β1, and pSmad2/3), and increased Smad7 gene expression. Finally, TSF decreased the expressions of wnt1, active-β-catenin, FN, and MMP7 to regulate the Wnt/β-catenin pathway. Taken together, TSF seems to attenuate myocardial fibrosis in KKAy mice by inhibiting TGF-β/Smad2/3 and Wnt/β-catenin signaling pathways.