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This study aims to investigate the regulatory role of PAX interacting protein 1 (PTIP) in modulating proliferation, angiogenesis, and inflammatory responses in RMECs under high-glucose conditions. The levels of PTIP, VEGF, MDA, and SOD were measured in RMECs cultured under both normal and high-glucose conditions. A PTIP overexpression vector and a PTIP interference vector were constructed and transfected into RMECs exposed to high glucose. Cell proliferation was assessed using the CCK-8 assay, cell migration capacity was evaluated through wound healing assays, and tube formation ability was analyzed using Matrigel-based assays. Intracellular MDA and SOD levels were determined biochemically, while TNF-\u03b1 and IL-6 concentrations in the culture supernatants were quantified by ELISA. The expression levels of EGR3, VEGF, MMP3, and MMP9 were detected using Western blotting and immunofluorescence techniques. The results showed that the expressions of PTIP and SOD were down-regulated in RMECs exposed to high glucose, whereas the levels of VEGF and MDA were up-regulated. Overexpression of PTIP in high-glucose-treated RMECs significantly suppressed cell proliferation, tube formation, and migration abilities. Additionally, it markedly reduced the levels of MDA, IL-6, TNF-\u03b1, EGR3, VEGF, MMP3, and MMP9 while increasing the level of SOD. Conversely, PTIP knockdown in RMECs under high-glucose conditions elicited opposite effects. Thus, overexpression of PTIP mitigated the impairment of proliferation, migration, and tube formation abilities, as well as reduced the inflammatory response induced by high glucose in RMECs.<\/jats:p>","DOI":"10.1007\/s11626-025-01143-x","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T18:40:39Z","timestamp":1767984039000},"page":"57-68","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["PTIP inhibits proliferation, migration, and angiogenesis of retinal microvascular endothelial cells in a high-glucose environment"],"prefix":"10.1007","volume":"62","author":[{"given":"Jinfeng","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhua","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiting","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"1143_CR1","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1001\/jamaophthalmol.2024.3283","volume":"142","author":"AF Alsoudi","year":"2024","unstructured":"Alsoudi AF, Wai KM, Koo E, Parikh R, Mruthyunjaya P, Rahimy E (2024) Initial therapy of panretinal photocoagulation vs anti-VEGF injection for proliferative diabetic retinopathy. 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