{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:40:48Z","timestamp":1792615248138,"version":"4.5.0"},"reference-count":77,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["802201219"],"award-info":[{"award-number":["802201219"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:p>\n                    Choroidal neovascularization (CNV) is characterized by the infiltration of immune cells, particularly neutrophils. Neutrophil extracellular trap (NET) facilitates the angiogenesis of pulmonary endothelial cells via activating Toll\u2010like receptor 4 (TLR4). TLR4 promotes the expression of transcription factor hypoxia inducible factor\u20101\u03b1 (HIF\u20101\u03b1), which promotes inflammation and angiogenesis via the up\u2010regulation of metalloproteinase\u20109 (MMP\u20109) and interleukin\u20101\u03b2 (IL\u20101\u03b2). In the present study, we aimed to identify the formation of NET and its role in CNV. Our results showed that NET levels were increased in a mouse laser\u2010induced CNV model via oxidative stress, whereas the inhibition of NET alleviated CNV.\n                    <jats:italic>In\u2009vitro<\/jats:italic>\n                    , NET activated the TLR4\/HIF\u20101\u03b1 pathway in human choroidal endothelial cells (HCECs). Additionally, NET increased the transcription and expression of MMP\u20109 and IL\u20101\u03b2 in HCECs via activating the TLR4\/HIF\u20101\u03b1 pathway. Meanwhile, NET promoted the inflammatory response accompanied by the proliferation, migration and tube formation of HCECs in a MMP\u20109\u2010 and IL\u20101\u03b2\u2010dependent manner. In conclusion, NET was up\u2010regulated in CNV and promoted the formation of CNV via activating the TLR4\/HIF\u20101\u03b1 pathway in choroidal endothelial cells. Our data uncovered the novel role of NET in promoting the formation of CNV. The underlying mechanism of NET could be targeted to delay the process of CNV.\n                  <\/jats:p>","DOI":"10.1111\/febs.16928","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T10:03:20Z","timestamp":1691489000000},"page":"5395-5410","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Neutrophil extracellular traps boost laser\u2010induced mouse choroidal neovascularization through the activation of the choroidal endothelial cell TLR4\/HIF\u20101\u03b1 pathway"],"prefix":"10.1111","volume":"290","author":[{"given":"Jia","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of Pathogen Biology, Medical College Nantong University  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Suzhou Municipal Hospital The Affiliated Suzhou Hospital of 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