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M2 macrophages produce vascular endothelial growth factor (VEGF), which aggravates CNV formation. The histone acetyltransferase p300 enhances the stability of spliced X\u2010box binding protein 1 (XBP1s) and promotes the transcriptional activity of the XBP1s target gene homocysteine inducible endoplasmic reticulum protein with ubiquitin\u2010like domain 1 (Herpud1). Herpud1 promotes the M2 polarization of macrophages. This study aimed to explore the roles of the p300\/XBP1s\/Herpud1 axis in the polarization of macrophages and the pathogenesis of CNV. Hypoxia\u2010induced p300 interacted with XBP1s to acetylate XBP1s in RAW264.7 cells. Additionally, hypoxia\u2010induced p300 enhanced the XBP\u20101s\u2010mediated unfolded protein response (UPR), alleviated the proteasome\u2010dependent degradation of XBP1s and enhanced the transcriptional activity of XBP1s for Herpud1. The hypoxia\u2010induced p300\/XBP1s\/Herpud1 axis facilitated RAW264.7 cell M2 polarization. Knockdown of the p300\/XBP1s\/Herpud1 axis in RAW264.7 cells inhibited the proliferation, migration and tube formation of mouse choroidal endothelial cells (MCECs). The p300\/XBP1s\/Herpud1 axis increased in infiltrating M2\u2010type macrophages in mouse laser\u2010induced CNV lesions. Blockade of the p300\/XBP1s\/Herpud1 axis inhibited macrophage M2 polarization and alleviated CNV lesions. Our study demonstrated that the p300\/XBP1s\/Herpud1 axis in infiltrating macrophages increased the M2 polarization of macrophages and the development of CNV.<\/jats:p>","DOI":"10.1111\/jcmm.16673","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T05:22:07Z","timestamp":1622438527000},"page":"6709-6720","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["The P300\/XBP1s\/Herpud1 axis promotes macrophage M2 polarization and the development of choroidal neovascularization"],"prefix":"10.1111","volume":"25","author":[{"given":"Wendie","family":"Li","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Ningbo Eye Hospital Ningbo 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 Nanjing Medical 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