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Using a sciatic nerve injury model, we assessed nerve function using the sciatic nerve function index. We analyzed the expression levels of EGFL7, forkhead box proteins A1 (FOXA1), nerve growth factor (NGF), brain\u2010derived neurotrophic factors (BDNF), Neurofilament 200 (NF200), myelin protein zero (P0), cell adhesion molecule 1 (CD31), vascular endothelial growth factor (VEGF), and NOTCH\u2010related proteins in tissues and cells. Cell proliferation, migration, and angiogenesis were evaluated through cell counting kit assays, 5\u2010ethynyl\u20102\u2032deoxyuridine staining, and Transwell assays. We investigated the binding of FOXA1 to the EGFL7 promoter using dual\u2010luciferase assays and chromatin immunoprecipitation. We observed decreased EGFL7 expression and increased FOXA1 expression in PNI, and EGFL7 overexpression alleviated gastrocnemius muscle atrophy, increased muscle weight, and improved motor function. Additionally, EGFL7 overexpression enhanced Schwann cell and endothelial cell proliferation and migration, promoted tube formation, and upregulated NGF, BDNF, NF200, P0, CD31, and VEGF expression. FOXA1 was found to bind to the EGFL7 promoter region, inhibiting EGFL7 expression and activating the NOTCH signaling pathway. Notably, FOXA1 overexpression counteracted the effects of EGFL7 on Schwann cells and endothelial cells. In conclusion, EGFL7 holds promise as a therapeutic molecule for treating sciatic nerve injury.<\/jats:p>","DOI":"10.1002\/cbin.12221","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T05:49:46Z","timestamp":1722404986000},"page":"1698-1713","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Overexpression of EGFL7 promotes angiogenesis and nerve regeneration in peripheral nerve injury"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4406-3883","authenticated-orcid":false,"given":"Zengtao","family":"Hao","sequence":"first","affiliation":[{"name":"Area A, Hand\u2010Foot Microsurgery Center, The Second Affiliated Hospital of Inner Mongolia Medical University Hohhot China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqi","family":"Huo","sequence":"additional","affiliation":[{"name":"Area A, Hand\u2010Foot Microsurgery Center, 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