{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T01:30:00Z","timestamp":1777512600228,"version":"3.51.4"},"reference-count":37,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770279, 82070280, 81770266"],"award-info":[{"award-number":["81770279, 82070280, 81770266"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"a major project of Natural Science Research in Jiangsu Higher Education Institutions","award":["18KJA310005"],"award-info":[{"award-number":["18KJA310005"]}]},{"name":"the Six Talent Peaks Project in Jiangsu Province","award":["2018-WSN-062"],"award-info":[{"award-number":["2018-WSN-062"]}]},{"name":"a Science and Technology Project of Taicang City","award":["TC2019KJFZ02"],"award-info":[{"award-number":["TC2019KJFZ02"]}]},{"name":"a Science and Technology Project of Nantong City","award":["MS22020006"],"award-info":[{"award-number":["MS22020006"]}]},{"name":"Clinical Medical Research Center of Cardiothoracic Diseases in Nantong","award":["HS2019001"],"award-info":[{"award-number":["HS2019001"]}]},{"name":"Innovation Team of Cardiothoracic Disease in Nantong University","award":["TECT-A04"],"award-info":[{"award-number":["TECT-A04"]}]},{"name":"Nantong Key Laboratory of Translational Medicine of Cardiothoracic Diseases","award":["\/"],"award-info":[{"award-number":["\/"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u03bcM) 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 \u03b1-smooth muscle actin (\u03b1-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.<\/jats:p>","DOI":"10.3390\/ijms222111893","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T12:39:42Z","timestamp":1635856782000},"page":"11893","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Necroptosis Inhibition by Hydrogen Sulfide Alleviated Hypoxia-Induced Cardiac Fibroblasts Proliferation via Sirtuin 3"],"prefix":"10.3390","volume":"22","author":[{"given":"Yue","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiwei","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengting","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jieru","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingxian","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahai","family":"Shi","sequence":"additional","affiliation":[{"name":"Nantong Key Laboratory of Translational Medicine in Cardiothoracic Diseases, Research Institution of Translational Medicine in Cardiothoracic Diseases, Nantong University, Nantong 226001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8523-6543","authenticated-orcid":false,"given":"Guoliang","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2501","DOI":"10.1053\/j.jvca.2019.10.005","article-title":"The Pathophysiology of Myocardial Ischemia and Perioperative Myocardial Infarction","volume":"34","author":"Smit","year":"2020","journal-title":"J. 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