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Original Article

Korean J Physiol Pharmacol 2023; 27(1): 1-8

Published online January 1, 2023

Copyright © Korean J Physiol Pharmacol.

Hydrogen sulfide alleviates hypothyroidism-induced myocardial fibrosis in rats through stimulating autophagy and inhibiting TGF-β1/Smad2 pathway

Xiong Song1,#, Liangui Nie1,#, Junrong Long2, Junxiong Zhao1, Xing Liu1, Liuyang Wang1, Da Liu1, Sen Wang1, Shengquan Liu1,*, and Jun Yang1,*

1Department of Cardiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, 2Department of Cardiology, The People's Hospital of Shuangfeng County, Loudi, Hunan 417700, China

Correspondence to:Shengquan Liu
Jun Yang

#These authors contributed equally to this work.

Author contributions: Conceived and designed the experiments: X.S., L.N., J.L., J.Z., X.L., L.W., D.L., S.W., S.L., and J.Y. All authors read and approved the final manuscript.

Received: August 23, 2021; Revised: December 28, 2021; Accepted: January 5, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Hypothyroidism alone can lead to myocardial fibrosis and result in heart failure, but traditional hormone replacement therapy does not improve the fibrotic situation. Hydrogen sulfide (H2S), a new gas signaling molecule, possesses anti-inflammatory, antioxidant, and anti-fibrotic capabilities. Whether H2S could improve hypothyroidism-induced myocardial fibrosis are not yet studied. In our study, H2S could decrease collagen deposition in the myocardial tissue of rats caused by hypothyroidism. Furthermore, in hypothyroidism-induced rats, we found that H2S could enhance cystathionine-gamma-lyase (CSE), not cystathionine β-synthase (CBS), protein expressions. Finally, we noticed that H2S could elevate autophagy levels and inhibit the transforming growth factor-β1 (TGF-β1) signal transduction pathway. In conclusion, our experiments not only suggest that H2S could alleviate hypothyroidism-induced myocardial fibrosis by activating autophagy and suppressing TGF-β1/SMAD family member 2 (Smad 2) signal transduction pathway, but also show that it can be used as a complementary treatment to conventional hormone therapy.

Keywords: Autophagy, Fibrosis, Hydrogen sulfide (H2S), Hypothyroidism, Transforming growth factor beta1