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

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.

• Publication year

  1993

• Venue

  Korean Journal of Physiology and Pharmacology

• Publication date

  1993-06-30

• Fields of study

  Medicine, Environmental Science

• Identifiers
  DOI 10.4196/kjpp.2023.27.1.1PMID 36575928PMCID 9806643
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Astragaloside IV Attenuates the Myocardial Injury Caused by Adriamycin by Inhibiting Autophagy

  2021cited by this paper
• Autophagy in the Diabetic Heart: A Potential Pharmacotherapeutic Target in Diabetic Cardiomyopathy.

  2021cited by this paper
• Thyroid Function and the Risk of Fibrosis of the Liver, Heart, and Lung in Humans: A Systematic Review and Meta-Analysis

  2020cited by this paper
• Hydrogen Sulfide Reverses LPS-Induced Behavioral Deficits by Suppressing Microglial Activation and Promoting M2 Polarization

  2020cited by this paper
• Self-eating: friend or foe? The emerging role of autophagy in fibrotic diseases

  2020cited by this paper
• Hydrogen Sulfide Treatment Improves Post-Infarct Remodeling and Long-Term Cardiac Function in CSE Knockout and Wild-Type Mice

  2020cited by this paper
• Exogenous hydrogen sulfide inhibits apoptosis by regulating endoplasmic reticulum stress-autophagy axis and improves myocardial reconstruction after acute myocardial infarction.

  2020cited by this paper
• Hydrogen sulfide inhibits aortic valve calcification in heart via regulating RUNX2 by NF-κB, a link between inflammation and mineralization

  2020cited by this paper
• QiShenYiQi pill improves the reparative myocardial fibrosis by regulating autophagy

  2020cited by this paper
• Salvanic acid B inhibits myocardial fibrosis through regulating TGF-β1/Smad signaling pathway.

  2019cited by this paper
• Netrin-1 plays a role in the effect of moderate exercise on myocardial fibrosis in rats

  2019cited by this paper
• Induction of LOX by TGF‐β1/Smad/AP‐1 signaling aggravates rat myocardial fibrosis and heart failure

  2019cited by this paper
• Trehalose-Induced Activation of Autophagy Improves Cardiac Remodeling After Myocardial Infarction.

  2018cited by this paper
• Hydrogen sulfide attenuates myocardial fibrosis in diabetic rats through the JAK/STAT signaling pathway

  2018cited by this paper
• Hydrogen Sulfide Regulating Myocardial Structure and Function by Targeting Cardiomyocyte Autophagy

  2018cited by this paper
• Beclin-1-Dependent Autophagy Protects the Heart During Sepsis

  2018cited by this paper
• Subclinical Hypothyroidism and the Risk of Cardiovascular Disease and All-Cause Mortality: A Meta-Analysis of Prospective Cohort Studies

  2018cited by this paper
• p62-mediated phase separation at the intersection of the ubiquitin-proteasome system and autophagy

  2018cited by this paper
• Myocardial fibrosis.

  2018cited by this paper
• Fibroblast-specific TGF-β-Smad2/3 signaling underlies cardiac fibrosis.

  2017cited by this paper
• Thyroid-stimulating hormone stimulation downregulates autophagy and promotes apoptosis in chondrocytes.

  2017influential reference
• Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation

  2017cited by this paper
• EphrinB2 Regulates Cardiac Fibrosis Through Modulating the Interaction of Stat3 and TGF-&bgr;/Smad3 Signaling

  2017cited by this paper
• Entanglement of GSK-3β, β-catenin and TGF-β1 signaling network to regulate myocardial fibrosis.

  2017cited by this paper
• Autophagy-regulating protease Atg4: structure, function, regulation and inhibition

  2017cited by this paper
• Hypothyroidism and the Heart.

  2017cited by this paper
• Effects of hydrogen sulfide on myocardial fibrosis and PI3K/AKT1-regulated autophagy in diabetic rats.

  2016cited by this paper
• Activation of SIRT3 by resveratrol ameliorates cardiac fibrosis and improves cardiac function via the TGF-β/Smad3 pathway.

  2015cited by this paper
• Hydrogen sulfide as a potent cardiovascular protective agent.

  2014cited by this paper
• Hypothyroidism and Its Rapid Correction Alter Cardiac Remodeling

  2014influential reference
• H2S Inhibits Hyperglycemia-Induced Intrarenal Renin-Angiotensin System Activation via Attenuation of Reactive Oxygen Species Generation

  2013cited by this paper
• Nox4 modulates collagen production stimulated by transforming growth factor β1 in vivo and in vitro.

  2013cited by this paper
• Inhibition of NADPH oxidase 4-related signaling by sodium hydrosulfide attenuates myocardial fibrotic response.

  2013cited by this paper
• XBP1 mRNA Splicing Triggers an Autophagic Response in Endothelial Cells through BECLIN-1 Transcriptional Activation*

  2012cited by this paper
• Rescue of mesangial cells from high glucose-induced over-proliferation and extracellular matrix secretion by hydrogen sulfide.

  2011cited by this paper
• LC3 and Autophagy.

  2008cited by this paper
• Autophagy fights disease through cellular self-digestion

  2008cited by this paper
• How to Interpret LC3 Immunoblotting

  2007cited by this paper
• Atg5 and Bcl-2 provide novel insights into the interplay between apoptosis and autophagy

  2007cited by this paper
• Chronic sodium hydrosulfide treatment decreases medial thickening of intramyocardial coronary arterioles, interstitial fibrosis, and ROS production in spontaneously hypertensive rats.

  2007cited by this paper
• Low Thyroid Function Leads to Cardiac Atrophy With Chamber Dilatation, Impaired Myocardial Blood Flow, Loss of Arterioles, and Severe Systolic Dysfunction

  2005cited by this paper
• [Myocardial fibrosis].

  1996cited by this paper

• A Causal Relationship Between Hypothyroidism and Gestational Hypertension: Results From a Two-Sample Mendelian Randomization Analysis.

  2025cites this paper
• Crosstalk Between H2S and Hormones: The Bilateral Relationship and Molecular Mechanisms.

  2025cites this paper
• Hydrogen sulfide revisited: a stealthy ally in the unseen war against cardiovascular disease.

  2025cites this paper
• Dusp14-Mediated Dephosphorylation of MLKL Protects Against Cardiomyocyte Necroptosis in Hypothyroidism-Induced Heart Failure.

  2025cites this paper
• Hydrogen Sulfide and Irisin, Potential Allies in Ensuring Cardiovascular Health

  2024cites this paper
• Combined levothyroxine and testosterone treatment for restoring erectile dysfunction in propylthiouracil-induced hypothyroid rats.

  2023cites this paper
• Primary Hypothyroidism and Alzheimer’s Disease: A Tale of Two

  2023cites this paper
• Biomarkers of Atrial Fibrillation Recurrence in Patients with Paroxysmal or Persistent Atrial Fibrillation Following External Direct Current Electrical Cardioversion

  2023cites this paper
• Hydrogen Sul fi de and Irisin, Potential Allies in Ensuring Cardiovascular Health

  year unknowncites this paper