{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T22:41:13Z","timestamp":1785451273333,"version":"3.56.0"},"reference-count":0,"publisher":"American Diabetes Association","license":[{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Chronic, non-healing skin wounds such as diabetic foot ulcers (DFUs) are common in patients with type 2 diabetes. Here, we investigated the role of chemokine CCL28 and its receptor CCR10 in downregulation of endothelial nitric oxide synthase (eNOS) in association with delayed skin wound healing in the db\/db mouse model of type 2 diabetes. We observed reduced eNOS expression and elevated CCL28\/CCR10 levels in dorsal skin of db\/db mice and subdermal leg biopsies from human subjects with type 2 diabetes. Further interrogation revealed that overexpression of CCR10 reduced eNOS expression, NO bioavailability, and tube formation of human dermal microvascular endothelial cells (HDMVECs) in vitro which was recapitulated in mouse dorsal skin. In addition, incubation of HDMVECs with CCL28 led to internalization of the CCR10\/eNOS complex and co-localization with lysosome-associated membrane protein-1. Finally, topical application of myristoylated CCR10 binding domain 7 amino acid (Myr-CBD7) peptide prevented CCR10-eNOS interaction and subsequent eNOS downregulation, enhanced eNOS\/NO levels, eNOS\/VEGF-R2+ microvessel density, and blood perfusion, reduced inflammatory cytokine levels, and importantly, decreased wound healing time in db\/db mice. Thus, endothelial cell CCR10 activation in genetically obese mice with type 2 diabetes promotes eNOS depletion and endothelial dysfunction, and targeted disruption of CCR10\/eNOS interaction improves wound healing.<\/jats:p>","DOI":"10.2337\/db21-1108","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T07:58:48Z","timestamp":1658995128000},"update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":5,"title":["Inhibition of CCL28\/CCR10-mediated eNOS Downregulation Improves Skin Wound Healing in the Obesity-induced Mouse Model of Type 2 Diabetes"],"prefix":"10.2337","author":[{"given":"Zhenlong","family":"Chen","sequence":"first","affiliation":[{"name":"1Departments of Anesthesiology, University of Illinois at Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob M.","family":"Haus","sequence":"additional","affiliation":[{"name":"2School of Kinesiology, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"3Departments of Periodontics, University of Illinois at Chicago, Chicago, IL, USA"},{"name":"4Departments of the Center for Wound Healing and Tissue Regeneration, University of Illinois at Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Jiang","sequence":"additional","affiliation":[{"name":"5Departments of Pharmacology and Regenerative Medicine, University of Illinois at Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Sverdlov","sequence":"additional","affiliation":[{"name":"6Departments of Research Histology and Tissue Imaging Collaborative, University of Illinois at Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa A.","family":"DiPietro","sequence":"additional","affiliation":[{"name":"3Departments of Periodontics, University of Illinois at Chicago, Chicago, IL, USA"},{"name":"4Departments of the Center for Wound Healing and Tissue Regeneration, University of Illinois at Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Xiong","sequence":"additional","affiliation":[{"name":"7Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health, Science Center at San Antonio, San Antonio, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie C.","family":"Wu","sequence":"additional","affiliation":[{"name":"8Departments of Surgery and Stem Cell and Regenerative Medicine, Center for Lower Extremity, Ambulatory Research, Dr. William M. Scholl College of Podiatric Medicine, Rosalind Franklin, University of Medicine and Science, North Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Koh","sequence":"additional","affiliation":[{"name":"4Departments of the Center for Wound Healing and Tissue Regeneration, University of Illinois at Chicago, Chicago, IL, USA"},{"name":"9Departments of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Minshall","sequence":"additional","affiliation":[{"name":"1Departments of Anesthesiology, University of Illinois at Chicago, Chicago, IL, USA"},{"name":"5Departments of Pharmacology and Regenerative Medicine, University of Illinois at Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2022,7,28]]},"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/doi\/10.2337\/db21-1108\/686293\/db211108.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/doi\/10.2337\/db21-1108\/686293\/db211108.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T12:44:57Z","timestamp":1667393097000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/doi\/10.2337\/db21-1108\/147325\/Inhibition-of-CCL28-CCR10-mediated-eNOS"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,28]]},"references-count":0,"URL":"https:\/\/doi.org\/10.2337\/db21-1108","relation":{"has-preprint":[{"id-type":"doi","id":"10.2337\/figshare.20360037","asserted-by":"object"},{"id-type":"doi","id":"10.2337\/figshare.20360037.v1","asserted-by":"object"}]},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,28]]},"article-number":"db211108"}}