Exogenous H(2)S mitigates myocardial fibrosis in diabetic rats through suppression of the canonical Wnt pathway

Hydrogen sulfide (H(2)S) has antifibrotic activity in the kidneys, heart, lungs, and other organs. The present study investigated the protective activity of exogenous H(2)S against myocardial fibrosis in a rat model of diabetes. Animals were assigned to normal control, diabetes mellitus (DM), DM + sodium hydrosulfide (NaHS; DM + NaHS) and NaHS groups. Fasting blood glucose (FBG), cardiac function and hydroxyproline were monitored. Heart histomorphology and ultrastructure were additionally evaluated. Wnt1-inducible signaling pathway protein (WISP)-1 protein expression in the myocardium was determined by immunohistochemical staining. Matrix metalloprotease (MMP)-2, tissue inhibitor of metalloproteinase (TIMP)-2, collagens, and canonical Wnt and transforming growth factor (TGF)-β1/SMAD family member 3 (Smad3) pathway-related proteins were assessed by western blotting. Cardiac function was decreased, and myocardial injury, hypertrophy and fibrosis were increased in the diabetes model rats. MMP-2 expression was decreased, and the expressions of WISP-1, TIMP-2, collagens, and canonical Wnt and TGF-β1/Smad3 pathway-related proteins were increased in the myocardia of the diabetes model rats. The present results indicated that the canonical Wnt pathway promoted diabetic myocardial fibrosis by upregulating the TGF-β1/Smad3 pathway. Except for FBG, exogenous H(2)S ameliorated the changes in diabetes-associated indices in rats in the DM + NaHS group. The results are consistent with H(2)S protection of streptozotocin-induced myocardial fibrosis in the diabetes model rats by downregulation of the canonical Wnt and TGF-β1/Smad3 pathway and decreased myocardial collagen deposition.