{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T12:24:47Z","timestamp":1787574287670,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Myocardial ischemia\u2013reperfusion injury (MIRI) remains a major clinical problem, and its regulatory mechanisms are not fully defined. This study aimed to identify key MIRI\u2010related targets and clarify their roles in cellular and animal models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Differentially expressed genes in MIRI were screened using the GEO dataset GSE6381, and core genes were identified through protein\u2013protein interaction analysis and weighted gene co\u2010expression network analysis. External datasets GSE249812 and GSE123342 were used to validate core gene expression. Transcription factors regulating cystic fibrosis transmembrane conductance regulator (CFTR) were predicted using the KnockTF database. In AC16 cells, an oxygen\u2013glucose deprivation\/reoxygenation (OGD\/OGR) model was established. Microphthalmia\u2010associated transcription factor (MITF) was knocked down or overexpressed, CFTR was silenced or overexpressed, and cell viability, proliferation, apoptosis, and NO\/L\u2010arginine\/citrulline levels were assessed. The MITF\u2010CFTR interaction was examined by dual\u2010luciferase assay and chromatin immunoprecipitation\u2010quantitative PCR (ChIP\u2010qPCR). A rat ischemia\u2013reperfusion (I\/R) model was used to evaluate the effects of MITF silencing and CFTR rescue on cardiac injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 42 core genes related to MIRI were identified. CFTR showed consistent upregulation across datasets and was linked to pathways including arginine biosynthesis. CFTR\u2010related transcription factors included MITF, TP53, and STAT3, but ChIP\u2010qPCR showed detectable enrichment only for MITF at the CFTR promoter. In AC16 cells, CFTR protein increased during early reoxygenation. OGD\/OGR elevated CFTR and MITF, while MITF knockdown or CFTR silencing further reduced cell viability and proliferation, increased apoptosis, and was accompanied by lower NO and citrulline levels and higher L\u2010arginine levels. MITF overexpression showed the opposite trend, and CFTR overexpression partially reversed the effects of MITF deficiency. In\u00a0vivo, MITF knockdown aggravated cardiac dysfunction, increased CK and CK\u2010MB levels, worsened tissue injury, and elevated cleaved caspase\u20103 after I\/R, whereas CFTR overexpression partly improved these changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MITF regulates CFTR expression in MIRI, and disruption of the MITF\u2010CFTR axis is associated with aggravated injury in cellular and animal models. Restoring CFTR partially mitigates MITF deficiency\u2010related damage. These findings support the involvement of MITF\u2010CFTR regulation in MIRI and provide a basis for further mechanistic investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jgm.70102","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T02:41:23Z","timestamp":1786070483000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MITF Regulates CFTR Expression to Participate in Myocardial Ischemia\u2013Reperfusion Injury"],"prefix":"10.1002","volume":"28","author":[{"given":"Baoxin","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Cardiology, Shanghai East Hospital Tongji University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenying","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Heart Failure, Shanghai East Hospital Tongji University School of Medicine  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