{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T03:52:49Z","timestamp":1788925969598,"version":"build-2803163510"},"reference-count":44,"publisher":"American Society for Clinical Investigation","issue":"23","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AR060562,NR015649,NR013881"],"award-info":[{"award-number":["AR060562,NR015649,NR013881"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100012186","name":"Wound Healing Foundation","doi-asserted-by":"crossref","award":["3M Healthcare fellowship,Medline Research Grant Innovation Awar"],"award-info":[{"award-number":["3M Healthcare fellowship,Medline Research Grant Innovation Awar"]}],"id":[{"id":"10.13039\/100012186","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001797","name":"PhRMA Foundation","doi-asserted-by":"crossref","award":["Research Starter Grant"],"award-info":[{"award-number":["Research Starter Grant"]}],"id":[{"id":"10.13039\/100001797","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006686","name":"University of Miami","doi-asserted-by":"crossref","award":["SAC-2013-19,SAC-2016-9R1"],"award-info":[{"award-number":["SAC-2013-19,SAC-2016-9R1"]}],"id":[{"id":"10.13039\/100006686","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12,5]]},"abstract":"<jats:p>Diabetic foot ulcers (DFUs) are a life-threatening disease that often results in lower limb amputations and a shortened life span. Current treatment options are limited and often not efficacious, raising the need for new therapies. To investigate the therapeutic potential of topical statins to restore healing in patients with DFUs, we performed next-generation sequencing on mevastatin-treated primary human keratinocytes. We found that mevastatin activated and modulated the EGF signaling to trigger an antiproliferative and promigratory phenotype, suggesting that statins may shift DFUs from a hyperproliferative phenotype to a promigratory phenotype in order to stimulate healing. Furthermore, mevastatin induced a migratory phenotype in primary human keratinocytes through EGF-mediated activation of Rac1, resulting in actin cytoskeletal reorganization and lamellipodia formation. Interestingly, the EGF receptor is downregulated in tissue biopsies from patients with DFUs. Mevastatin restored EGF signaling in DFUs through disruption of caveolae to promote keratinocyte migration, which was confirmed by caveolin-1 (Cav1) overexpression studies. We conclude that topical statins may have considerable therapeutic potential as a treatment option for patients with DFUs and offer an effective treatment for chronic wounds that can be rapidly translated to clinical use.<\/jats:p>","DOI":"10.1172\/jci.insight.129320","type":"journal-article","created":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T12:01:57Z","timestamp":1572350517000},"source":"Crossref","is-referenced-by-count":53,"title":["Mevastatin promotes healing by targeting caveolin-1 to restore EGFR signaling"],"prefix":"10.1172","volume":"4","author":[{"given":"Andrew P.","family":"Sawaya","sequence":"first","affiliation":[{"name":"Wound Healing and Regenerative Medicine Research Program, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, and"},{"name":"Molecular and Cellular Pharmacology Graduate Program in Biomedical Sciences, University of Miami Miller School of Medicine, Miami, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Jozic","sequence":"additional","affiliation":[{"name":"Wound Healing and Regenerative Medicine Research Program, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rivka C.","family":"Stone","sequence":"additional","affiliation":[{"name":"Wound Healing and Regenerative Medicine Research Program, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0197-6198","authenticated-orcid":true,"given":"Irena","family":"Pastar","sequence":"additional","affiliation":[{"name":"Wound Healing and Regenerative Medicine Research Program, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andjela N.","family":"Egger","sequence":"additional","affiliation":[{"name":"Wound Healing and Regenerative Medicine Research Program, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivera","family":"Stojadinovic","sequence":"additional","affiliation":[{"name":"Wound Healing and Regenerative Medicine Research Program, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, and"},{"name":"Immunology, Infection and Inflammation Graduate Program, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7866-2774","authenticated-orcid":true,"given":"George D.","family":"Glinos","sequence":"additional","affiliation":[{"name":"Wound Healing and Regenerative Medicine Research Program, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6824-9844","authenticated-orcid":true,"given":"Robert S.","family":"Kirsner","sequence":"additional","affiliation":[{"name":"Wound Healing and Regenerative Medicine Research Program, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, and"},{"name":"Wound Healing Clinical Research Program, University of Miami Hospital, University of Miami Health System, Miami, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjana","family":"Tomic-Canic","sequence":"additional","affiliation":[{"name":"Wound Healing and Regenerative Medicine Research Program, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, and"},{"name":"Molecular and Cellular Pharmacology Graduate Program in Biomedical Sciences, University of Miami Miller School of Medicine, Miami, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2019,12,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009337"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-475X.2009.00543.x"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-014-0081-9"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.7547\/0980489"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32169"},{"issue":"1","key":"B6","doi-asserted-by":"crossref","first-page":"1.e1","DOI":"10.1016\/j.jaad.2013.06.055","article-title":"Diabetic foot ulcers: Part I. 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