{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:33:22Z","timestamp":1788863602242,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:00:00Z","timestamp":1722988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["2P50 AR060780"],"award-info":[{"award-number":["2P50 AR060780"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR080950"],"award-info":[{"award-number":["AR080950"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Rarefaction of blood and lymphatic vessels in the skin has been reported in systemic sclerosis (SSc) (scleroderma). E26 transformation\u2013specific\u2013related factor (ERG) and Friend leukemia virus\u2013induced erythroleukemia 1 (FLI\u20101) are important regulators of angiogenesis, but their role in lymphatic vasculature is lesser known. The goal of this study was to determine the role of ERG and FLI\u20101 in postnatal lymphangiogenesis and SSc lymphatic system defects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Immunofluorescence was used to detect ERG and FLI\u20101 in skin biopsy samples from patients with SSc and healthy controls. Transcriptional analysis of ERG or FLI\u20101\u2013silenced human dermal lymphatic endothelial cells (LECs) was performed using microarrays. Effects of ERG and FLI\u20101 deficiency on in vitro tubulogenesis in human dermal LECs were examined using a Matrigel assay. ERG and FLI\u20101 endothelial\u2013specific knockouts and ERG lymphatic\u2013specific knockouts were generated to examine vessel regeneration in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ERG and FLI\u20101 protein levels were reduced in the blood and lymphatic vasculature in SSc skin biopsy samples. ERG levels were shown to regulate genes involved in lymphatic vessel specification, including vascular endothelial growth factor receptor 3\/FLT\u20104, lymphatic vessel endothelial hyaluronan receptor 1, SOX\u201018, and prospero homeobox 1 (PROX\u20101), whereas FLI\u20101 enhanced the function of ERG. The ERG\u2013FLT\u20104 pathway regulated in vitro tubulogenesis in human LECs. Deficiency of ERG or FLI\u20101 similarly impaired the function of blood vessels in mice. However, only ERG deficiency affected the regeneration of lymphatic vessels during wound healing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>ERG and FLI\u20101 are essential regulators of blood and lymphatic vessel regeneration. Deficiency of ERG and FLI\u20101 in SSc endothelial cells may contribute to the impairment of blood and lymphatic vasculature in patients with SSc.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42944-toc-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42944","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:34:50Z","timestamp":1720139690000},"page":"1645-1657","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>ERG<\/scp> Regulates Lymphatic Vessel Specification Genes and Its Deficiency Impairs Wound Healing\u2010Associated 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