{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T15:13:17Z","timestamp":1783437197925,"version":"3.54.6"},"reference-count":54,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:00:00Z","timestamp":1657756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91849130"],"award-info":[{"award-number":["91849130"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Ischemic stroke is a leading cause of human mortality and long\u2010term disability worldwide. As one of the main forms of regulator of calcineurin 1 (RCAN1), the contribution of RCAN1.4 in diverse biological and pathological conditions has been implicated. But the role of RCAN1.4 in ischemic stroke progression remains elusive. This study is to explore the expression changes and roles of RCAN1.4 in ischemic stroke as well as the underlying mechanisms for these changes and effects of RCAN1.4 in ischemic stroke.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Middle cerebral artery occlusion model in C57BL\/6J mice and oxygen\u2013glucose deprivation (OGD) model in primary astrocytes were performed to induce the cerebral ischemic stroke. The expression pattern of RCAN1.4 was assessed using real\u2010time quantitative PCR and western blotting in\u00a0vivo and in\u00a0vitro. Mechanistically, the underlying mechanism for the elevation of RCAN1.4 in the upstream was investigated. Lentiviruses were administrated, and the effect of RCAN1.4 in postischemic inflammation was clearly clarified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here we uncovered that RCAN1.4 was dramatically increased in mouse ischemic brains and OGD\u2010induced primary astrocytes. HIF1\u03b1, activated upon OGD, significantly upregulated RCAN1.4 gene expression through specifically binding to the RCAN1.4 promoter region and activating its promoter activity. The functional hypoxia\u2010responsive element (HRE) was located between \u2212254 and \u2212245\u2009bp in the RCAN1.4 promoter region. Moreover, elevated RCAN1.4 alleviated the release of pro\u2010inflammatory cytokines TNF\u03b1, IL1\u03b2, IL6 and reduced expression of iNOS, COX2 in primary astrocytes upon OGD, whereas RCAN1.4 silencing has the opposite effect. Of note, RCAN1.4 overexpression inhibited OGD\u2010induced NF\u2010\u03baB activation in primary astrocytes, leading to decreased degradation of I\u03baB\u03b1 and reduced nuclear translocation of NF\u2010\u03baB\/p65.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our results reveal a novel mechanism underscoring the upregulation of RCAN1.4 by HIF1\u03b1 and the protective effect of RCAN1.4 against postischemic inflammation, suggesting its significance as a promising therapeutic target for ischemic stroke treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51624","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T05:05:43Z","timestamp":1657861543000},"page":"1224-1240","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Upregulation of <scp>RCAN1<\/scp>.4 by <scp>HIF1\u03b1<\/scp> alleviates <scp>OGD<\/scp>\u2010induced inflammatory response in astrocytes"],"prefix":"10.1002","volume":"9","author":[{"given":"Xiaxin","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurology Qilu Hospital of Shandong University  Jinan Shandong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Radiology Qilu Hospital of Shandong University  Jinan Shandong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin","family":"Wang","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Otorhinolaryngology Qilu Hospital of Shandong University  Jinan Shandong Province China"},{"name":"Department of Otorhinolaryngology Qilu Hospital of Shandong University  Jinan Shandong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhao","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Otorhinolaryngology Qilu Hospital of Shandong University  Jinan Shandong Province China"},{"name":"Department of Otorhinolaryngology Qilu Hospital of Shandong University  Jinan Shandong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8206-1346","authenticated-orcid":false,"given":"Xiulian","family":"Sun","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Otorhinolaryngology Qilu Hospital of Shandong University  Jinan Shandong Province China"},{"name":"Brain Research Institute Qilu Hospital of Shandong University  Jinan Shandong Province China"},{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission Qilu Hospital of Shandong University  Jinan Shandong Province 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