{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:43:05Z","timestamp":1792456985042,"version":"4.5.0"},"reference-count":62,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5K08HL129072\u201004"],"award-info":[{"award-number":["5K08HL129072\u201004"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Wound Repair Regeneration"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Impaired lower extremity wound healing due to diabetes presents a significant societal burden, as 25% of diabetic wounds lead to major amputations. While TGF\u2010\u03b2 has been extensively studied in diabetic wound healing, the role of \u03b2II spectrin (SPTBN1), a known adapter of SMAD3 in the canonical TGF\u2010\u03b2 signalling pathway, remains unexplored. Single\u2010cell RNA sequencing analysis revealed an increase in\n                    <jats:italic>SPTBN1<\/jats:italic>\n                    expression in endothelial cells from non\u2010diabetic skin to diabetic skin and ulcers. We found that silencing\n                    <jats:italic>SPTBN1<\/jats:italic>\n                    in human umbilical vein endothelial cells (HUVECs) suppressed endothelial sprouting and tube formation. Based on these findings, we hypothesised that SPTBN1 regulates diabetic wound healing by modulating angiogenesis. To test this, we created\n                    <jats:italic>Sptbn1<\/jats:italic>\n                    endothelial\u2010specific conditional knockout (\n                    <jats:italic>Sptbn1<\/jats:italic>\n                    <jats:sup>ECKO<\/jats:sup>\n                    ) mice and used the well\u2010established streptozocin\u2010induced diabetic excisional dorsal wound model. Interestingly, while\n                    <jats:italic>Sptbn1<\/jats:italic>\n                    <jats:sup>ECKO<\/jats:sup>\n                    mice showed delayed wound healing, the delay was not due to impaired angiogenesis, but rather due to excessive inflammation. Inflammation persisted in\n                    <jats:italic>Sptbn1<\/jats:italic>\n                    <jats:sup>ECKO<\/jats:sup>\n                    mice when it resolved in controls, as evidenced by higher numbers of neutrophils, inflammatory monocytes and greater iNOS staining intensity in the wound beds. Additionally,\n                    <jats:italic>Sptbn1<\/jats:italic>\n                    <jats:sup>ECKO<\/jats:sup>\n                    wounds had significantly less granulation tissue and fewer fibroblasts in the regenerative phase. Collectively, these findings suggest that \u03b2II spectrin in endothelial cells is a potential therapeutic target in chronic diabetic wound healing.\n                  <\/jats:p>","DOI":"10.1111\/wrr.70103","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T05:38:46Z","timestamp":1761716326000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Endothelial\n                    <scp>\u03b2II<\/scp>\n                    Spectrin Deletion Exacerbates Inflammation and Impairs Tissue Regeneration in Ischemic\u2013Diabetic Skin Wound Healing"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9271-9138","authenticated-orcid":false,"given":"Ruchi","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Surgery School of Medicine and Health Sciences, The George Washington University  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula O.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine School of Medicine and Health Sciences, The George Washington University  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Chai","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine School of Medicine and Health Sciences, The George Washington University  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pritham","family":"Mulagura","sequence":"additional","affiliation":[{"name":"Department of Surgery School of Medicine and Health Sciences, The George Washington University  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean M.","family":"Lee","sequence":"additional","affiliation":[{"name":"Office of Clinical Research, The George Washington University  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Theocharidis","sequence":"additional","affiliation":[{"name":"Department of Surgery Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton N.","family":"Sidawy","sequence":"additional","affiliation":[{"name":"Department of Surgery School of Medicine and Health Sciences, The George Washington University  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett A.","family":"Shook","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine School of Medicine and Health Sciences, The George Washington University  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao\u2010Ngoc","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Surgery School of Medicine and Health Sciences, The George Washington University  Washington DC USA"},{"name":"Department of Biochemistry and Molecular Medicine School of Medicine and Health Sciences, The George Washington University  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/dci22-0043"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-2176"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/2042018817744513"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/12971"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000430221"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-4585"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208946"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1075994"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.52375"},{"key":"e_1_2_9_11_1","volume-title":"Revealing the Organ\u2010Specific Expression of SPTBN1 Using Single\u2010Cell RNA 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