Exogenous H2S mitigates myocardial fibrosis in diabetic rats through suppression of the canonical Wnt pathway

Yang,Rui; Jia,Qiang; Ma,Shan‑Feng; Wang,Ya; Mehmood,Shomaila; Chen,Yan

doi:10.3892/ijmm.2019.4237

Exogenous H2S mitigates myocardial fibrosis in diabetic rats through suppression of the canonical Wnt pathway

Authors:
- Rui Yang
- Qiang Jia
- Shan‑Feng Ma
- Ya Wang
- Shomaila Mehmood
- Yan Chen
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Affiliations: School of Life Sciences, Anhui University, Hefei, Anhui 230601, P.R. China, Department of Physiology, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China
Published online on: June 10, 2019 https://doi.org/10.3892/ijmm.2019.4237
Pages: 549-558
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hydrogen sulfide (H2S) has antifibrotic activity in the kidneys, heart, lungs, and other organs. The present study investigated the protective activity of exogenous H2S 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 H2S ameliorated the changes in diabetes‑associated indices in rats in the DM + NaHS group. The results are consistent with H2S 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.

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