{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:38:27Z","timestamp":1792165107682,"version":"4.4.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T00:00:00Z","timestamp":1708300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL109561"],"award-info":[{"award-number":["R01 HL109561"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01 AR067182"],"award-info":[{"award-number":["R01 AR067182"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"Ingalls Foundation, Cleveland OH","doi-asserted-by":"publisher","award":["Medof Immunology"],"award-info":[{"award-number":["Medof Immunology"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>How reparative processes are coordinated following injury is incompletely understood. In recent studies, we showed that autocrine C3a and C5a receptor (C3ar1 and C5ar1) G protein\u2013coupled receptor signaling plays an obligate role in vascular endothelial growth factor receptor 2 growth signaling in vascular endothelial cells. We documented the same interconnection for platelet-derived growth factor receptor growth signaling in smooth muscle cells, epidermal growth factor receptor growth signaling in epidermal cells, and fibroblast growth factor receptor signaling in fibroblasts, indicative of a generalized cell growth regulatory mechanism. In this study, we examined one physiological consequence of this signaling circuit. We found that disabling CD55 (also known as decay accelerating factor), which lifts restraint on autocrine C3ar1\/C5ar1 signaling, concomitantly augments the growth of each cell type. The mechanism is heightened C3ar1\/C5ar1 signaling resulting from the loss of CD55\u2019s restraint jointly potentiating growth factor production by each cell type. Examination of the effect of lifted CD55 restraint in four types of injury (burn, corneal denudation, ear lobe puncture, and reengraftment of autologous skin) showed that disabled CD55 function robustly accelerated healing in all cases, whereas disabled C3ar1\/C5ar1 signaling universally retarded it. In wild-type mice with burns or injured corneas, applying a mouse anti-mouse CD55 blocking Ab (against CD55\u2019s active site) to wounds accelerated the healing rate by 40\u201370%. To our knowledge, these results provide new insights into mechanisms that underlie wound repair and open up a new tool for accelerating healing.<\/jats:p>","DOI":"10.4049\/jimmunol.2300628","type":"journal-article","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T14:43:37Z","timestamp":1708353817000},"page":"1142-1149","source":"Crossref","is-referenced-by-count":6,"title":["Critical Role of CD55 in Controlling Wound Healing"],"prefix":"10.1093","volume":"212","author":[{"given":"Lorna","family":"Kang","sequence":"first","affiliation":[{"name":"Institute of Pathology, Case Western Reserve University , Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7398-9786","authenticated-orcid":false,"given":"Maryo","family":"Kohen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Case Western Reserve University , Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Case Western Reserve University , Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4950-6275","authenticated-orcid":false,"given":"Emma","family":"Hammelef","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Case Western Reserve University , Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae Suk","family":"Kim","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Case Western Reserve University , Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Bapputty","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Case Western Reserve University , Cleveland, OH"},{"name":"Department of Pediatrics, Rainbow Babies Hospitals, Cleveland Medical Center , Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose","family":"Gubitosi-Klug","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Case Western Reserve University , Cleveland, OH"},{"name":"Department of Pediatrics, Rainbow Babies Hospitals, Cleveland Medical Center , Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5095-6401","authenticated-orcid":false,"given":"Faruk H","family":"Orge","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Case Western Reserve University , Cleveland, OH"},{"name":"Department of Pediatrics, Rainbow Babies Hospitals, Cleveland Medical Center , Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Kern","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University , Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5239-2518","authenticated-orcid":false,"given":"M Edward","family":"Medof","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Case Western Reserve University , Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,2,19]]},"reference":[{"key":"2025020405473077900_r1","doi-asserted-by":"crossref","first-page":"e39540","DOI":"10.1371\/journal.pone.0039540","article-title":"Blocking fibroblast growth factor receptor signaling inhibits tumor growth, lymphangiogenesis, and metastasis","volume":"7","author":"Larrieu-Lahargue","year":"2012","journal-title":"PLoS One"},{"key":"2025020405473077900_r2","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1096\/fj.03-1179fje","article-title":"VEGF-A promotes tissue repair-associated lymphatic vessel formation via VEGFR-2 and the alpha1beta1 and alpha2beta1 integrins","volume":"18","author":"Hong","year":"2004","journal-title":"FASEB J."},{"key":"2025020405473077900_r3","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1096\/fj.201900677R","article-title":"RTK signaling requires C3ar1\/C5ar1 and IL-6R joint signaling to repress dominant PTEN, SOCS1\/3 and PHLPP restraint","volume":"34","author":"Strainic","year":"2020","journal-title":"FASEB J."},{"key":"2025020405473077900_r4","doi-asserted-by":"crossref","first-page":"jcs219352","DOI":"10.1242\/jcs.219352","article-title":"VEGFR2 survival and mitotic signaling depends on joint activation of associated C3ar1\/C5ar1 and IL-6R-gp130","volume":"132","author":"Hwang","year":"2019","journal-title":"J Cell Sci"},{"key":"2025020405473077900_r5","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s40472-019-0224-2","article-title":"Role of complement activation in allograft inflammation","volume":"6","author":"Chun","year":"2019","journal-title":"Curr. 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