Hydrogen Sulfide Alleviates Skeletal Muscle Fibrosis via Attenuating Inflammation and Oxidative Stress

Zhao, Linlin; Liu, Xiaoguang; Zhang, Jing; Dong, Gaoyang; Xiao, Wu; Xu, Xin

doi:10.3389/fphys.2020.533690

Cited by 28 publications

(19 citation statements)

References 43 publications

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“…Previous studies have suggested that H 2 S alleviated the skeletal muscle fibrosis and partly improved skeletal muscle injury via oxidative stress inhibition [23]. Doxorubicininduced myocardial fibrosis was significantly attenuated by H 2 S via suppressing ROS production [24].…”

Section: Discussionmentioning

confidence: 96%

Necroptosis Inhibition by Hydrogen Sulfide Alleviated Hypoxia-Induced Cardiac Fibroblasts Proliferation via Sirtuin 3

Zhang

Gong

Meng

et al. 2021

IJMS

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Myocardial ischemia or hypoxia can induce myocardial fibroblast proliferation and myocardial fibrosis. Hydrogen sulfide (H2S) is a gasotransmitter with multiple physiological functions. In our present study, primary cardiac fibroblasts were incubated with H2S donor sodium hydrosulfide (NaHS, 50 μM) for 4 h followed by hypoxia stimulation (containing 5% CO2 and 1% O2) for 4 h. Then, the preventive effects on cardiac fibroblast proliferation and the possible mechanisms were investigated. Our results showed that NaHS reduced the cardiac fibroblast number, decreased the hydroxyproline content; inhibited the EdU positive ratio; and down-regulated the expressions of α-smooth muscle actin (α-SMA), the antigen identified by monoclonal antibody Ki67 (Ki67), proliferating cell nuclear antigen (PCNA), collagen I, and collagen III, suggesting that hypoxia-induced cardiac fibroblasts proliferation was suppressed by NaHS. NaHS improved the mitochondrial membrane potential and attenuated oxidative stress, and inhibited dynamin-related protein 1 (DRP1), but enhanced optic atrophy protein 1 (OPA1) expression. NaHS down-regulated receptor interacting protein kinase 1 (RIPK1) and RIPK3 expression, suggesting that necroptosis was alleviated. NaHS increased the sirtuin 3 (SIRT3) expressions in hypoxia-induced cardiac fibroblasts. Moreover, after SIRT3 siRNA transfection, the inhibitory effects on cardiac fibroblast proliferation, oxidative stress, and necroptosis were weakened. In summary, necroptosis inhibition by exogenous H2S alleviated hypoxia-induced cardiac fibroblast proliferation via SIRT3.

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Section: Discussionmentioning

confidence: 96%

Necroptosis Inhibition by Hydrogen Sulfide Alleviated Hypoxia-Induced Cardiac Fibroblasts Proliferation via Sirtuin 3

Zhang

Gong

Meng

et al. 2021

IJMS

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“…Our previous study has found that H 2 S alleviates renal injury and fibrosis in response to unilateral ureteral obstruction by attenuating macrophage infiltration ( Zhou et al, 2020 ). In addition, H 2 S donors are also found to alleviate bleomycin-induced lung fibrosis ( Du et al, 2019 ), transverse aortic constriction-induced myocardial fibrosis ( Liu et al, 2021 ) and blunt contusion-induced skeletal muscle fibrosis ( Zhao L et al, 2020 ) by attenuating oxidative stress. Consistent with these findings, the present study found that both GYY4137 and NaHS significantly decreased immobilization-induced leukocyte infiltration and oxidative stress, reduced the production of IL-1β and TGF-β in skeletal muscles, thus alleviating immobilization-induced muscle fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…Administration of NaHS at high dose of 10 mg/kg has been shown to induce lung inflammation by itself, and also to worsen CLP-induced lung inflammation ( Zhang et al, 2006 ). However, administration of NaHS at low dose of 0.5–2 mg/kg exerts anti-inflammatory effects in animal models of ovalbumin-induced airway inflammation ( Benetti et al, 2013 ), homocysteine-induced neuro-inflammatory conditions ( Kumar and Sandhir, 2019 ) and blunt contusion-induced skeletal muscle atrophy ( Zhao L et al, 2020 ). In consistent with these studies, our findings showed that both GYY4137 (50 mg/kg) and NaHS (20 μM/kg or 1.12 mg/kg) significantly inhibited immobilization-induced inflammation in skeletal muscles.…”

Section: Discussionmentioning

confidence: 99%

H2S Protects Against Immobilization-Induced Muscle Atrophy via Reducing Oxidative Stress and Inflammation

Liu

Bao

et al. 2022

Front. Physiol.

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Chronic inflammation and oxidative stress are major triggers of the imbalance between protein synthesis and degradation during the pathogenesis of immobilization-induced muscle atrophy. This study aimed to elucidate the effects of hydrogen sulfide (H2S), a gas transmitter with potent anti-inflammatory and antioxidant properties, on immobilization-induced muscle atrophy. Mice were allocated to control and immobilization (IM) groups, which were treated with slow (GYY4137) or rapid (NaHS) H2S releasing donors for 14 days. The results showed that both GYY4137 and NaHS treatment reduced the IM-induced muscle loss, and increased muscle mass. The IM-induced expressions of Muscle RING finger 1 (MuRF1) and atrogin-1, two muscle-specific E3 ubiquitin ligases, were decreased by administration of GYY4137 or NaHS. Both GYY4137 and NaHS treatments alleviated the IM-induced muscle fibrosis, as evidenced by decreases in collagen deposition and levels of tissue fibrosis biomarkers. Moreover, administration of GYY4137 or NaHS alleviated the IM-induced infiltration of CD45 + leukocytes, meanwhile inhibited the expressions of the pro-inflammatory biomarkers in skeletal muscles. It was found that administration of either GYY4137 or NaHS significantly attenuated immobilization-induced oxidative stress as indicated by decreased H2O2 levels and 8-hydroxy-2′-deoxyguanosine (8-OHdG) immunoreactivity, as well as increased total antioxidant capacity (T-AOC), nuclear factor erythroid-2-related factor 2 (NRF2) and NRF2 downstream anti-oxidant targets levels in skeletal muscles. Collectively, the present study demonstrated that treatment with either slow or rapid H2S releasing donors protected mice against immobilization-induced muscle fibrosis and atrophy. The beneficial effects of H2S on immobilization-induced skeletal muscle atrophy might be due to both the anti-inflammatory and anti-oxidant properties of H2S.

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“…H 2 S donors have been widely used in vivo using animal models to treat various pathological conditions (Fagone et al, 2018). This includes reduction by the H 2 S donor NaHS of skeletal muscle atrophy in a mouse model of diabetes (Lu et al, 2020), or the decrease of muscle fibrosis after contusion-induced injury (Zhao et al, 2020). Interestingly, various therapeutics like Zofenopril have been shown to exert their effect through the indirect release of H 2 S (Fagone et al, 2018; Wallace et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…H 2 S has emerged as a promoter of the resolution of inflammation through the regulation of macrophage inflammatory state (Sun et al, 2020; Wallace et al, 2012). Interestingly, H 2 S-releasing molecules, like NaHS, have been shown to reduce skeletal muscle atrophy in a mouse model of diabetes (Lu et al, 2020) and to decrease muscle fibrosis after contusion-induced injury (Zhao et al, 2020). Moreover, H 2 S-releasing molecules have shown promising results in cardiovascular disorders and arthritis with reduced adverse effects (Wallace et al, 2020; Wallace et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Myofiber / pro-inflammatory macrophage interplay controls muscle damage in mdx mice

Saclier

Larbi

Moulin

et al. 2020

Preprint

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SummaryDuchenne Muscular Dystrophy is a genetic muscle disease characterized by chronic inflammation and fibrosis, which is mediated by a pro-fibrotic macrophage population expressing pro-inflammatory markers. The aim of this study was to characterize cellular events leading to the alteration of macrophage properties, and to modulate macrophage inflammatory status using the gaseous mediator H2S. We first analyzed the relationship between myofibers and macrophages in the mdx mouse model of Duchenne Muscular Dystrophy using coculture experiments. We showed that normal myofibers derived from mdx mice strongly skewed the polarization of resting macrophages towards a pro-inflammatory phenotype. Treatment of mdx mice with NaHS, an H2S donor, reduced the number of pro-inflammatory macrophages in skeletal muscle, which was associated with a decrease in the number of nuclei per fiber, a reduction of myofiber branching and a reduced fibrosis. These results identify an interplay between myofibers and macrophages where dystrophic myofibers contribute to the maintenance of a highly inflammatory environment that skews the macrophage status, which in turn favors myofiber damage, myofiber branching and fibrosis establishment. They also identify H2S donors as a potential therapeutic strategy to improve dystrophic muscle phenotype by modulating macrophage inflammatory status.

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Hydrogen Sulfide Alleviates Skeletal Muscle Fibrosis via Attenuating Inflammation and Oxidative Stress

Cited by 28 publications

References 43 publications

Necroptosis Inhibition by Hydrogen Sulfide Alleviated Hypoxia-Induced Cardiac Fibroblasts Proliferation via Sirtuin 3

Necroptosis Inhibition by Hydrogen Sulfide Alleviated Hypoxia-Induced Cardiac Fibroblasts Proliferation via Sirtuin 3

H2S Protects Against Immobilization-Induced Muscle Atrophy via Reducing Oxidative Stress and Inflammation

Myofiber / pro-inflammatory macrophage interplay controls muscle damage in mdx mice

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