{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:25:26Z","timestamp":1753878326036,"version":"3.41.2"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Retinopathy of prematurity is characterised by abnormal retinal neovascularization in response to hypoxia stress. Prolyl 4\u2010hydroxylase domain protein 3 (PHD3) is a well\u2010known molecular oxygen sensor. However, the role that PHD3 plays in retinopathy of prematurity remains unclear. In this work, a mouse model of oxygen\u2010induced retinopathy (OIR) was used for in\u00a0vivo studies. Compared with the mice in room air, OIR mice showed sprouting of retinal neovascularization and increased level of PHD3. It was further found that PHD3 overexpression weakened OIR\u2010induced retinal neovascularization and promoted cell apoptosis in the retina, indicating a mitigative effect on retinopathy. More importantly, OIR\u2010induced upregulation of hypoxia inducible factor\u20101 alpha (HIF\u20101\u03b1) and vascular endothelial growth factor (VEGFA) was offset by PHD3 overexpression. In in\u00a0vitro experiments, mouse retinal microvascular endothelial cells (MRMECs) were cultured under hypoxic conditions. The functions of endothelial cells including cell proliferation, cell migration, and tube formation ability were suppressed by PHD3, suggesting an anti\u2010angiogenesis effect of PHD3. In line with in\u00a0vivo experiments, the expression of HIF\u20101\u03b1 and VEGFA levels declined in endothelial cells when PHD3 was overexpressed. Taken together, PHD3 alleviates retinopathy of prematurity through anti\u2010angiogenesis, and the core mechanism may involve cell apoptosis of retina endothelial cell and HIF\u20101\u03b1\u2013VEGFA axis. These findings provide exciting new insights into the pathogenesis of retinopathy of prematurity, and could offer new treatment directions.<\/jats:p>","DOI":"10.1111\/1440-1681.70020","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T04:40:21Z","timestamp":1738903221000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>PHD3<\/scp>\u2010Mediated Inhibition of Retinal Neovascularization in\u00a0Retinopathy of Prematurity"],"prefix":"10.1111","volume":"52","author":[{"given":"Jiawei","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Heilongjiang Hospital, Beijing Children's Hospital, Capital Medical University The Sixth Affiliated Hospital of Harbin Medical University  Harbin P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haifeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The First Hospital of Qiqihar The Affiliated Qiqihar Hospital of Southern Medical University  Qiqihar P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Heilongjiang Hospital, Beijing Children's Hospital, Capital Medical University The Sixth Affiliated Hospital of Harbin Medical University  Harbin P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The First Hospital of Qiqihar The Affiliated Qiqihar Hospital of Southern Medical University  Qiqihar P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60178-6"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aaa8695"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-007-9066-0"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000330174"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23010350"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2015-3218"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.701516"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-09-114561"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2008.10"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2012-0330"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206955200"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308862200"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00507-4"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/1947601911423654"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2014.10.009"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.01.007"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2020.10.011"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110349"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2007.123125"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.2.3"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.187"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.09.043"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2014.07.050"},{"issue":"8","key":"e_1_2_9_25_1","first-page":"723","article-title":"Expression and Function of Delta\u2010Like Ligand 4 in a Rat Model of Retinopathy of Prematurity","volume":"8","author":"Shi S.","year":"2013","journal-title":"Neural Regeneration Research"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11091490"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-1876"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43273"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.5114\/aoms.2013.36987"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2021.113777"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-023-00655-0"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2013.03.005"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-1474"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-01425-6"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-8-117"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1177\/1947601911423031"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-02-767293"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-014-1030-3"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep43935"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers10120496"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.129398"}],"container-title":["Clinical and Experimental Pharmacology and Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1440-1681.70020","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T09:20:00Z","timestamp":1741771200000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1440-1681.70020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,6]]},"references-count":40,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1111\/1440-1681.70020"],"URL":"https:\/\/doi.org\/10.1111\/1440-1681.70020","archive":["Portico"],"relation":{},"ISSN":["0305-1870","1440-1681"],"issn-type":[{"type":"print","value":"0305-1870"},{"type":"electronic","value":"1440-1681"}],"subject":[],"published":{"date-parts":[[2025,2,6]]},"assertion":[{"value":"2024-04-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70020"}}