Resveratrol ameliorates myocardial fibrosis by regulating Sirt1/Smad3 deacetylation pathway in rat model with dilated cardiomyopathy

Chen, Qingquan; Zeng, Yu; Yang, Xiulin; Wu, Yue; Zhang, Shuyu; Huang, Shirong; Zhong, Yameng; Chen, Min

doi:10.1186/s12872-021-02401-y

Cited by 17 publications

(12 citation statements)

References 25 publications

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“…As previously reported, the SIRT1 signaling pathway is involved in the regulation of autophagy and apoptosis and has been studied as part of the mechanism of resveratrol in various diseases (Chen et al, 2022;Gomes et al, 2018;Nishigaki et al, 2022).…”

Section: Discussionmentioning

confidence: 94%

“…SIRT1 is a member of the class III histone deacetylase family that is distinctively dependent on nicotinamide adenine dinucleotide (NAD+) for catalytic reactions (Yousafzai, Jin, Ullah, & Wang, 2021); SIRT1 modulates gene expression, apoptosis, energy homeostasis, autophagy, acute stress responses, and mitochondrial biogenesis (Tovar‐Palacio, Noriega, & Mercado, 2022). Resveratrol is an agonist of SIRT1, so the activation of SIRT1 signaling is considered a key mechanism for its effects on a variety of diseases (Chen et al, 2022; Gomes et al, 2018; Nishigaki, Tsubokura, Tsuzuki‐Nakao, & Okada, 2022). Additionally, studies have also shown that the JNK pathway is a potential target of resveratrol (Shati, 2019; Wang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Resveratrol inhibits hepatic stellate cell activation by regulating autophagy and apoptosis through the SIRT1 and JNK signaling pathways

Zhang

Jian

Jiang

et al. 2022

Journal of Food Biochemistry

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Resveratrol, a natural polyphenol found in grapes, berries, peanuts, and medicinal plants, has previously been reported to have several biological activities, including inhibiting hepatic brosis. Hepatic stellate cell (HSC) activation is the major cellular source of matrix protein-secreting myo broblasts, which are the major drivers of liver brogenesis. Numerous studies on the protective effects of resveratrol against liver brosis have focused on the inhibition of HSC activation. Although the underlying mechanisms remain to be fully elucidated, autophagy and apoptosis regulation might be intimately related. The mouse HSC line JS1 was stimulated with resveratrol to assess the mechanism and relationship between autophagy and apoptosis. Resveratrol dose-dependently modulated JS1 cell viability. Moreover, resveratrol inhibited JS1 cell activation and induced autophagy and apoptosis. This anti brotic effect was attenuated when autophagy was inhibited using chloroquine (CQ) or 3-methyladenine (3-MA) or when apoptosis was inhibited using Z-VAD-FMK. Furthermore, whether the Sirtuin1 (SIRT1) and c-Jun N-terminal kinase (JNK) signaling pathways were associated with resveratrol-induced autophagy and apoptosis in JS1 cells was examined. The SIRT1 inhibitor EX527 reversed autophagy, and the JNK inhibitor SP600125 was able to reverse both autophagy and apoptosis induced by resveratrol. These ndings suggest that the SIRT1 and JNK signaling pathways may be involved in resveratrol-mediated inhibition of HSC activation by regulating autophagy and apoptosis. Materials And Methods Cells and cell cultureThe immortalized mouse HSC line JS1 was kindly provided by Professor Scott L. Friedman (Mt. Sinai School of Medicine, USA). JS1 cells were cultured in DMEM (Gibco; Thermo Fisher Scienti c, Inc.) supplemented with 10% FBS (Gibco; Thermo Fisher Scienti c, Inc.) and 1% penicillin/streptomycin at 5% CO 2 and 37°C. The medium was replaced with media supplemented with 0.5% FBS for 12 h prior to treatment. Different concentrations of resveratrol (cat. no. R5010; Sigma) was added to the medium and an incubated for different durations, according to the experimental design. JS1 cells were pretreated with 5 mM 3-methyladenine (3-MA; cat. no. M9281; Sigma-Aldrich; Merck KGaA), 30 µM chloroquine (CQ) diphosphate salt (cat. no. C6628; Sigma-Aldrich; Merck KGaA) or 20 µM Z-VAD-FMK (cat. no. C1202; Beyotime Institute of Biotechnology) for 2 h and 10 µM EX527 (cat. no. ab141506; Abcam) or 10 µM SP600125 (cat. no. ab120065; Abcam) for 1 h, followed by treatment with or without 50 µM resveratrol for 24 h. Each in vitro experiment was repeated three times. Measurement of JS1 cell viabilityCells were plated in plastic 96-well plates and incubated with 0.1, 1, 10, 50 or 100 µM resveratrol for 24 h. Subsequently, cell viability was assessed using an MTT Cell Proliferation and Cytotoxicity Assay kit (cat.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Resveratrol inhibits hepatic stellate cell activation by regulating autophagy and apoptosis through the SIRT1 and JNK signaling pathways

Zhang

Jian

Jiang

et al. 2022

Journal of Food Biochemistry

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“…In this model, KAT2B induces acetylation of SMAD2 and, subsequently, activates SMAD2 and the transforming growth factor β signaling pathway [ 39 ]. SMAD3 could also be acetylated during cardiac fibrosis [ 41 , 42 ]. Activation of SIRT1 by resveratrol [ 41 ], nicotinamide mononucleotide [ 42 ] or geniposide [ 70 ] could decrease SMAD3 acetylation and fibrosis.…”

Section: Implication Of Cardiac Acetylation In Metabolic Heart Diseasementioning

confidence: 99%

“…SMAD3 could also be acetylated during cardiac fibrosis [ 41 , 42 ]. Activation of SIRT1 by resveratrol [ 41 ], nicotinamide mononucleotide [ 42 ] or geniposide [ 70 ] could decrease SMAD3 acetylation and fibrosis. Moreover, inhibition of P300 appears to exert anti-fibrotic functions [ 82 ].…”

Section: Implication Of Cardiac Acetylation In Metabolic Heart Diseasementioning

confidence: 99%

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Cardiac Acetylation in Metabolic Diseases

et al. 2022

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Lysine acetylation is a highly conserved mechanism that affects several biological processes such as cell growth, metabolism, enzymatic activity, subcellular localization of proteins, gene transcription or chromatin structure. This post-translational modification, mainly regulated by lysine acetyltransferase (KAT) and lysine deacetylase (KDAC) enzymes, can occur on histone or non-histone proteins. Several studies have demonstrated that dysregulated acetylation is involved in cardiac dysfunction, associated with metabolic disorder or heart failure. Since the prevalence of obesity, type 2 diabetes or heart failure rises and represents a major cause of cardiovascular morbidity and mortality worldwide, cardiac acetylation may constitute a crucial pathway that could contribute to disease development. In this review, we summarize the mechanisms involved in the regulation of cardiac acetylation and its roles in physiological conditions. In addition, we highlight the effects of cardiac acetylation in physiopathology, with a focus on obesity, type 2 diabetes and heart failure. This review sheds light on the major role of acetylation in cardiovascular diseases and emphasizes KATs and KDACs as potential therapeutic targets for heart failure.

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