{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:09:02Z","timestamp":1787015342316,"version":"build-2736575974"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T00:00:00Z","timestamp":1610409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010881","name":"Suzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["SYS2018005"],"award-info":[{"award-number":["SYS2018005"]}],"id":[{"id":"10.13039\/501100010881","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010881","name":"Suzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["SYS2018060"],"award-info":[{"award-number":["SYS2018060"]}],"id":[{"id":"10.13039\/501100010881","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":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Wet age\u2010related macular degeneration (wAMD), characterized by choroidal neovascularization (CNV), is a leading cause of irreversible vision loss among elderly people in developed nations. Subretinal fibrosis, mediated by epithelial\u2010mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells, leads to unsuccessful anti\u2010vascular endothelial growth factor (VEGF) agent treatments in CNV patients. Under hypoxic conditions, hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1) increases the stability and activation of p53, which activates microRNA\u201034a (miRNA\u201034a) transcription to promote fibrosis. Additionally, Klotho is a target gene of miRNA\u201034a that inhibits fibrosis. This study aimed to explore the role of the HIF\u20101\u03b1\/p53\/miRNA\u201034a\/Klotho axis in subretinal fibrosis and CNV. Hypoxia\u2010induced HIF\u20101\u03b1 promoted p53 stability, phosphorylation and nuclear translocation in ARPE\u201019 cells (a human RPE cell line). HIF\u20101\u03b1\u2010dependent p53 activation up\u2010regulated miRNA\u201034a expression in ARPE\u201019 cells following hypoxia. Moreover, hypoxia\u2010induced p53\u2010dependent miRNA\u201034a inhibited the expression of Klotho in ARPE\u201019 cells. Additionally, the HIF\u20101\u03b1\/p53\/miRNA\u201034a\/Klotho axis facilitated hypoxia\u2010induced EMT in ARPE\u201019 cells. In vivo, blockade of the HIF\u20101\u03b1\/p53\/miRNA\u201034a\/Klotho axis alleviated the formation of mouse laser\u2010induced CNV and subretinal fibrosis. In short, the HIF\u20101\u03b1\/p53\/miRNA\u201034a\/Klotho axis in RPE cells promoted subretinal fibrosis, thus aggravating the formation of CNV.<\/jats:p>","DOI":"10.1111\/jcmm.16272","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T06:42:30Z","timestamp":1610692950000},"page":"1700-1711","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["The HIF\u20101\u03b1\/p53\/miRNA\u201034a\/Klotho axis in retinal pigment epithelial cells promotes subretinal fibrosis and exacerbates choroidal neovascularization"],"prefix":"10.1111","volume":"25","author":[{"given":"Laiqing","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Ophthalmology The Second Affiliated Hospital of Soochow University Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology 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