{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:58:35Z","timestamp":1792515515207,"version":"4.5.0"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T00:00:00Z","timestamp":1680652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of\u00a0Hunan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabet Med"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Diabetic foot ulcer (DFU) remains a serious chronic diabetic complication that can lead to disability. CircRNA\u2010itchy E3 ubiquitin protein ligase (circ\u2010ITCH) was observed to be down\u2010regulated in diabetic retinopathy and diabetic nephropathy, and overexpression of circ\u2010ITCH could inhibit the processes of these diseases. However, the detailed physiological and pathological functions of circ\u2010ITCH in wound healing of DFU remain undetermined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Exosomes derived from bone marrow stromal cells (BMSCs) were isolated and identified. Cell viability and angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated by cell counting kit\u20108 (CCK\u20108) and tube formation assays, respectively. The interplays of circ\u2010ITCH, TATA\u2010Box\u2010binding protein associated factor 15 (TAF15) and nuclear factor erythroid 2\u2010related factor 2 (Nrf2) mRNA were analysed by RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) combined immunofluorescent staining and RNA pull\u2010down assays. qRT\u2010PCR, western blot or immunohistochemistry (IHC) were used to measure the expression of circ\u2010ITCH, TAF15, Nrf2, vascular endothelial growth factor (VEGFR) and ferroptosis\u2010related makers. The mice DFU model was established to verify the in vitro results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Circ\u2010ITCH was down\u2010regulated in in vitro and in vivo models of DFU. Deferoxamine (DFO), an iron chelating agent, improved the viability and angiogenic ability of high glucose (HG)\u2010treated HUVECs. Overexpression of circ\u2010ITCH or co\u2010cultured with exosomal circ\u2010ITCH from BMSCs could alleviate HG\u2010induced ferroptosis and improve the angiogenesis ability of HUVECs. Circ\u2010ITCH in HUVECs recruited TAF15 protein to stabilize Nrf2 mRNA, thus activating the Nrf2 signalling pathway and suppressing ferroptosis. Exosomal circ\u2010ITCH from BMSCs also accelerated the wound healing process by inhibiting ferroptosis in the DFU mice in a time\u2010dependent manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Exosomal circ\u2010ITCH from BMSCs inhibited ferroptosis and improved the angiogenesis of HUVECs through activation of the Nrf2 signalling pathway by recruiting TAF15 protein, ultimately accelerating the wound healing process in DFU.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dme.15031","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T14:31:34Z","timestamp":1671546694000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":150,"title":["Bone marrow stromal cell\u2010derived exosomal circular RNA improves diabetic foot ulcer wound healing by activating the nuclear factor erythroid 2\u2010related factor 2 pathway and inhibiting ferroptosis"],"prefix":"10.1111","volume":"40","author":[{"given":"Juehao","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Xiangya Hospital of Central South University  Changsha China"},{"name":"Hunan Key Laboratory of Aging Biology, Xiangya Hospital Central South University  Changsha 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