{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T19:40:00Z","timestamp":1780774800699,"version":"3.54.1"},"reference-count":25,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Stem Cells and Development"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:p>\n                    Endothelial progenitor cells (EPCs) have the ability to form new blood vessels and protect ischemic tissues from damage. We previously reported that EPCs with low activity of aldehyde dehydrogenase (Alde-Low EPCs) possess the greater ability to treat ischemic tissues compared with Alde-High EPCs. The expression level of the hypoxia-inducible factors (HIFs), HIF-1\u03b1 and HIF-2\u03b1, was found to be greater in Alde-Low EPCs than in Alde-High EPCs. However, the precise role of the HIF factors in the regulation of EPC activity remains obscure. In this study, we demonstrate a critical role of HIF-2\u03b1 and its target gene CXCR4 for controlling the migratory activity of EPC to ischemic tissue. We found that coculture of Alde-High EPCs with microvesicles derived from Alde-Low EPCs improved their ability to repair an ischemic skin flap, and the expression of CXCR4 and its ligand SDF1 was significantly increased following the coculture. In Alde-Low EPCs, the expression of CXCR4 was suppressed by short hairpin RNA (shRNA)-mediated HIF-2\u03b1, but not HIF-1\u03b1 downregulation. Chromatin immunoprecipitation assays showed that HIF-2\u03b1, but not HIF-1\u03b1, binds to the promoter region of\n                    <jats:italic toggle=\"yes\">CXCR4<\/jats:italic>\n                    gene. The CXCR4 shRNA treatment in Alde-Low EPCs almost completely abrogated their migratory activity to ischemic tissues, whereas the reduction of vascular endothelial growth factor (VEGF) showed much less effect. The CXCR4 overexpression in Alde-High EPCs resulted in a partial, but significant improvement in their repairing ability in an ischemic skin flap. Collectively, these findings indicate that the CXCR4\/SDF-1 axis, which is specifically regulated by HIF-2\u03b1, plays a crucial role in the regulation of EPC migration to ischemic tissues.\n                  <\/jats:p>","DOI":"10.1089\/scd.2015.0290","type":"journal-article","created":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T05:05:45Z","timestamp":1448946345000},"page":"266-276","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":49,"title":["A Chemokine Receptor, CXCR4, Which Is Regulated by Hypoxia-Inducible Factor 2\u03b1, Is Crucial for Functional Endothelial Progenitor Cells Migration to Ischemic Tissue and Wound Repair"],"prefix":"10.1177","volume":"25","author":[{"given":"Tran Cam","family":"Tu","sequence":"first","affiliation":[{"name":"University of 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