{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:26:25Z","timestamp":1789593985547,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170109"],"award-info":[{"award-number":["82170109"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Lung ischemia\u2013reperfusion (I\/R) injury is a common complication following lung transplantation and cardiac surgery. This study aimed to investigate the role and underlying mechanisms involving Neurogenic locus notch homologue protein 1 (Notch1) signalling and microRNA\u2010485 (miR\u2010485) of hypoxia\u2010inducible factor 1\u2010alpha (HIF1\u03b1) in protecting pulmonary microvascular endothelial cells (PMVECs) against I\/R\u2010induced injury. We found that overexpression of HIF1\u03b1 significantly increased cell viability and decreased apoptosis in hypoxia\/reoxygenation (H\/R)\u2013treated PMVECs, while knockdown or inhibition of HIF1\u03b1 had the opposite effects. Moreover, HIF1\u03b1 overexpression activated the Notch1 signalling pathway by upregulating Hes1 mRNA expression and Hes1 promoter activity. Conversely, HIF1\u03b1 knockdown or inhibition inhibited Notch1 signalling. Furthermore, HIF1\u03b1 overexpression alleviated H\/R\u2010induced mitophagy and mitochondrial dysfunction. On the other hand, HIF1\u03b1 knockdown or inhibition aggravated mitophagy and mitochondrial dysfunction. We also found that HIF1\u03b1 transcriptionally activated the expression of miR\u2010485. Overexpression of miR\u2010485 reversed the detrimental effects of HIF1\u03b1 knockdown or inhibition on cell viability, apoptosis, Hes1 expression and mitophagy levels in H\/R\u2010treated PMVECs. Additionally, we identified NUMB endocytic adaptor protein (Numb) mRNA as a direct target of miR\u2010485, and miR\u2010485 overexpression suppressed Numb expression in PMVECs. In conclusion, these results suggest that targeting the HIF1\u03b1\u2010miR\u2010485\u2010Numb axis may be a potential therapeutic strategy for attenuating lung I\/R injury.<\/jats:p>","DOI":"10.1111\/jcmm.70965","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T09:13:49Z","timestamp":1767690829000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["HIF1\u03b1 Attenuated the Lung Ischemia\u2013Reperfusion Injury by Activating the miR\u2010485\/Notch1 Signalling"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6836-4340","authenticated-orcid":false,"given":"Shaohua","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery The First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Vascular Surgery The First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingchun","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery The First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery The First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunfan","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery The First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery The First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1438-9449","authenticated-orcid":false,"given":"Jian","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery The First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"issue":"9","key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1164\/rccm.202012-4306OC","article-title":"Obesity\u2010Related IL\u201018 Impairs T\u2010Regulatory Cell Function and Promotes Lung Ischemia\u2010Reperfusion Injury","volume":"204","author":"Akimova T.","year":"2021","journal-title":"American Journal of Respiratory and Critical Care Medicine"},{"issue":"1","key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"4173","DOI":"10.1038\/s41467-022-31811-5","article-title":"Reduction of Primary Graft Dysfunction Using Cytokine Adsorption During Organ Preservation and After Lung Transplantation","volume":"13","author":"Ghaidan H.","year":"2022","journal-title":"Nature Communications"},{"issue":"1","key":"e_1_2_12_4_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s13045-022-01292-6","article-title":"Hypoxia\u2010Inducible Factors: Master Regulators of Hypoxic Tumor Immune Escape","volume":"15","author":"Wu Q.","year":"2022","journal-title":"Journal of Hematology & Oncology"},{"issue":"5","key":"e_1_2_12_5_1","doi-asserted-by":"crossref","DOI":"10.3892\/mmr.2021.11991","article-title":"HIF\u20101alpha in Myocardial Ischemia\u2010Reperfusion Injury (Review)","volume":"23","author":"Zheng J.","year":"2021","journal-title":"Molecular Medicine Reports"},{"issue":"1","key":"e_1_2_12_6_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/resp.13722","article-title":"Hypoxia\u2010Inducible Factor and Bacterial Infections in Chronic Obstructive Pulmonary Disease","volume":"25","author":"Shukla S. 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