{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:09:29Z","timestamp":1792426169495,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T00:00:00Z","timestamp":1643241600000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>Increased neutrophil recruitment represents a hallmark event in myocardial ischemia\/reperfusion (I\/R) injury due to the ensuing inflammatory response. Circular RNAs (circRNAs) are important regulatory molecules involved in cell physiology and pathology. Herein, we analyzed the role of a novel circRNA circ_SMG6 in the regulation of neutrophil recruitment following I\/R injury, which may associate with the miR\u2010138\u20105p\/EGR1\/TLR4\/TRIF axis. Myocardial I\/R injury was modeled in vivo by ligation of the left anterior descending (LAD) artery followed by reperfusion in mice and in vitro by exposing a cardiomyocyte cell line (HL\u20101) to hypoxia\/reoxygenation (H\/R). Gain\u2010 and loss\u2010of\u2010function experiments were performed to evaluate the effect of the circ_SMG6\/miR\u2010138\u20105p\/EGR1\/TLR4\/TRIF axis on cardiac functions, myocardial infarction, myocardial enzyme levels, cardiomyocyte activities, and neutrophil recruitment. We found that the EGR1 expression was increased in myocardial tissues of I\/R mice. Knockdown of EGR1 was found to attenuate I\/R\u2010induced cardiac dysfunction and infarction area, pathological damage, and cardiomyocyte apoptosis. Mechanistic investigations showed that circ_SMG6 competitively bound to miR\u2010138\u20105p and consequently led to upregulation of EGR1, thus facilitating myocardial I\/R injury in mice and H\/R\u2010induced cell injury. Additionally, ectopic EGR1 expression augmented neutrophil recruitment and exacerbated the ensuing I\/R injury, which was related to the activated TLR4\/TRIF signaling pathway. Overall, our findings suggest that circ_SMG6 may deteriorate myocardial I\/R injury by promoting neutrophil recruitment via the miR\u2010138\u20105p\/EGR1\/TLR4\/TRIF signaling. This pathway may represent a potential therapeutic target in the management of myocardial I\/R injury.<\/jats:p>","DOI":"10.1155\/2022\/1927260","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:05:18Z","timestamp":1643328318000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Cardioprotective Effect of circ_SMG6 Knockdown against Myocardial Ischemia\/Reperfusion Injury Correlates with miR\u2010138\u20105p\u2010Mediated EGR1\/TLR4\/TRIF Inactivation"],"prefix":"10.1155","volume":"2022","author":[{"given":"Chen","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalun","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hualu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliang","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gongcheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9188-7940","authenticated-orcid":false,"given":"Jing","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,27]]},"reference":[{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.107819"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.3587"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/7018393"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-019-0756-8"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27384"},{"key":"e_1_2_8_6_2","first-page":"10107","article-title":"CircHIPK3 aggravates myocardial ischemia-reperfusion injury by binding to miRNA-124-3p","volume":"23","author":"Bai M.","year":"2019","journal-title":"European Review for Medical and Pharmacological Sciences"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2019.7976"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1177\/1559325820913786"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-016-1428-x"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1159\/000227809"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101616"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0044-101601"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14765"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103479"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/eci.12633"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI126428"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-019-0763-9"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-019-0768-4"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2020.02.003"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12354"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2507"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.11909\/j.issn.1671-5411.2020.05.004"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00155.2010"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05233.x"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101520"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S280315"},{"key":"e_1_2_8_27_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.27285"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2020.104430"},{"key":"e_1_2_8_29_2","first-page":"5355","article-title":"Metformin relieves acute respiratory distress syndrome by reducing miR-138 expression","volume":"22","author":"Yu L. L.","year":"2018","journal-title":"European Review for Medical and Pharmacological Sciences"},{"key":"e_1_2_8_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.27731"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-020-0809-z"},{"key":"e_1_2_8_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2014.51"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401320"},{"key":"e_1_2_8_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-019-0773-7"},{"key":"e_1_2_8_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-020-09720-2"},{"key":"e_1_2_8_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13228"}],"container-title":["Oxidative Medicine and Cellular Longevity"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2022\/1927260.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2022\/1927260.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2022\/1927260","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T01:54:43Z","timestamp":1748915683000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2022\/1927260"}},"subtitle":[],"editor":[{"given":"Dragan","family":"Hrn\u010di\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1155\/2022\/1927260"],"URL":"https:\/\/doi.org\/10.1155\/2022\/1927260","archive":["Portico"],"relation":{},"ISSN":["1942-0900","1942-0994"],"issn-type":[{"value":"1942-0900","type":"print"},{"value":"1942-0994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1]]},"assertion":[{"value":"2021-04-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1927260"}}