{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:25:07Z","timestamp":1790997907772,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T00:00:00Z","timestamp":1724630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Reperfusion strategies, the standard therapy for acute myocardial infarction (AMI), may result in ischemia\/reperfusion (I\/R) damage. Suppressor of cytokine signaling1 (SOCS1) exerts a cardioprotective function in myocardial I\/R damage. Here, we investigated epigenetic modulators that deregulate\u00a0SOCS1 in cardiomyocytes under hypoxia\/reoxygenation (H\/R) conditions. Human AC16 cardiomyocytes were exposed to H\/R conditions to generate a cell model of myocardial I\/R damage. Expression of mRNA and protein was detected by quantitative PCR and western blot analysis, respectively. Cell migratory and invasive abilities were evaluated by transwell assay. Cell apoptosis and M2 macrophage polarization were assessed by flow cytometry. TNF\u2010\u03b1, IL\u20101\u03b2, and IL\u20106 levels were examined by ELISA. The interaction of KLF4 with SOCS1 was verified by chromatin immunoprecipitation\u00a0and luciferase assays. SOCS1 and transcription factor KLF4 protein levels were underexpressed by 75% and 57%, respectively, in H\/R\u2010exposed AC16 cardiomyocytes versus control cells. Under H\/R conditions, forced SOCS1 expression (2.7 times) induced cell migration (2.2 times) and invasion (1.9 times) and hindered cell apoptosis (by 45%) of AC16 cardiomyocytes as well as enhanced M2 macrophage polarization (4.6 times). Mechanistically, KLF4 upregulation promoted SOCS1 transcription (2.6 times) and expression (2.6 times) by binding to the SOCS1 promoter. Decrease of SOCS1 (by 51%) reversed the effects of KLF4 upregulation on cardiomyocyte migration, invasion and apoptosis, and M2 macrophage polarization under H\/R conditions. Additionally, SOCS1 and KLF4 were underexpressed by 56% and 63%, respectively, in AMI serum. Our study indicates that KLF4\u2010induced upregulation of SOCS1 can attenuate H\/R\u2010triggered apoptosis of AC16 cardiomyocytes and enhance M2 macrophage polarization.<\/jats:p>","DOI":"10.1002\/jbt.23816","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T13:04:53Z","timestamp":1724677493000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["KLF4\u2010induced upregulation of SOCS1 ameliorates myocardial ischemia\/reperfusion injury by attenuating AC16 cardiomyocyte damage and enhancing M2 macrophage polarization"],"prefix":"10.1002","volume":"38","author":[{"given":"Jiming","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital,Hengyang Medical School University of South China Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital,Hengyang Medical School University of South China Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital,Hengyang Medical School University of South China Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunchen","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital,Hengyang Medical School University of South China Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5987-4510","authenticated-orcid":false,"given":"Junbi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital,Hengyang Medical School University of South China Hengyang 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