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with brain microvascular endothelial cells (BMECs) and neural stem cells (NSCs) and molecular interaction analyses, including DNA pull\u2010down and chromatin immunoprecipitation (ChIP), finding that RIPC significantly upregulated NTN4 expression in the ischemic penumbra of MCAO mice, that endothelial\u2010specific Ntn4 knockout abolished RIPC's protective effects\u2014impairing neurological recovery, angiogenesis and neurogenesis, which were rescued by recombinant NTN4 administration, that NTN4 promoted BMEC proliferation and tube formation via an integrin \u03b21\u2010PI3K\/AKT pathway while conditioned medium from Ntn4\u2010overexpressing BMECs enhanced NSC neuronal differentiation through an integrin \u03b21\u2010MAPK\/ERK axis, and that RIPC stabilised HIF\u20101\u03b1, which directly bound the Ntn4 promoter to drive its transcription, collectively establishing that RIPC orchestrates brain repair by stabilising HIF\u20101\u03b1 to transcriptionally activate endothelial NTN4, which signals through integrin \u03b21 to drive parallel PI3K\/AKT and MAPK\/ERK pathways for angiogenesis and neurogenesis, highlighting this axis as a key therapeutic target in stroke.<\/jats:p>","DOI":"10.1111\/jcmm.71121","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T04:21:54Z","timestamp":1775449314000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>HIF<\/scp>\n                    \u20101\u03b1\/Netrin\u20104 Axis Mediates\n                    <scp>RIPC<\/scp>\n                    \u2010Induced Angiogenesis and Neurogenesis After Ischemic Stroke"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2322-9297","authenticated-orcid":false,"given":"Zhaowei","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Neurology The Second Affiliated Hospital of Xuzhou Medical University  Xuzhou Jiangsu Province 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