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However, the underlying mechanism remains unclear. hUC\u2010MSCs\u2010Exos were identified by electron microscopy, NTA, and Western blotting. In the hypoxia\/reoxygenation (H\/R) cell model, human brain microvascular endothelial cells (HBMECs) were cocultured with hUC\u2010MSCs\u2010Exos. Then, cell viability, migration, apoptosis, and tube formation were measured by MTT, flow cytometry, transwell, and tube formation assays. RT\u2010qPCR and Western blotting were used to detect the changes in RNA and protein. RNA pull\u2010down and dual luciferase reporter assays confirmed the relationship between circDLGAP4, miR\u2010320, and KLF5. Ischemia\u2013reperfusion (I\/R) rat model was established for in vivo experiments. hUC\u2010MSCs\u2010Exos increased the expression levels of circDLGAP4 and KLF5 but decreased miR\u2010320 in H\/R\u2010treated HBMECs by transferring exosomal circDLGAP4. Knockdown of circDLGAP4 in hUC\u2010MSCs\u2010Exos reversed the promoting effects of hUC\u2010MSCs\u2010Exos on cell viability, migration, and tube formation in H\/R\u2010treated HBMECs in vitro and also abolished the protective effects of hUC\u2010MSCs\u2010Exos on cerebrovascular injury in I\/R rats. Mechanistically, exosomal circDLGAP4 negatively regulated miR\u2010320 in HBMECs, which directly bound to KLF5. In addition, the downregulation of miR\u2010320 could reverse the regulatory effect of exosomal shcircDLGAL5 in H\/R\u2010treated HBMECs by upregulating KLF5. hUC\u2010MSCs\u2010Exos\u2010derived circDLGAP4 reduced cerebrovascular injury by regulating miR\u2010320\/KLF5 signaling. These results provide a stem cell\u2010based approach to treat CIRI.<\/jats:p>","DOI":"10.1096\/fj.202201488r","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T11:27:51Z","timestamp":1675250871000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Human umbilical cord mesenchymal stem cells\u2010derived exosomal\n                    <scp>circDLGAP4<\/scp>\n                    promotes angiogenesis after cerebral ischemia\u2013reperfusion injury by regulating\n                    <scp>miR<\/scp>\n                    \u2010320\/\n                    <scp>KLF5<\/scp>\n                    axis"],"prefix":"10.1096","volume":"37","author":[{"given":"Jie","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University  Changsha P.R. 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