{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:24:51Z","timestamp":1792095891328,"version":"4.4.0"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T00:00:00Z","timestamp":1436832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The precise mechanisms of tissue fibrosis have not yet been elucidated in systemic sclerosis (<jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c). However, studies of the regulation of <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation, the most widely studied epigenetic mechanism, have confirmed the involvement of the <jats:styled-content style=\"fixed-case\">TET<\/jats:styled-content> family proteins, recently identified <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> demethylases, in the pathogenesis of <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c. The <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels of <jats:styled-content style=\"fixed-case\">TET<\/jats:styled-content> family members were compared in normal and <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c fibroblasts. The effects of hypoxia and si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> specific to <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101<jats:italic>\u03b1<\/jats:italic> on <jats:styled-content style=\"fixed-case\">TET<\/jats:styled-content> expression were also examined. Global methylation status was analysed by <jats:styled-content style=\"fixed-case\">LUMA<\/jats:styled-content>. The presence of 5\u2010hydroxymethylcytosine (5hmC) in <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c was examined by immunohistochemistry. The level of <jats:styled-content style=\"fixed-case\">TET<\/jats:styled-content>1 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c fibroblasts was elevated by 1.68 fold compared with that of normal fibroblasts, but the expression levels of <jats:styled-content style=\"fixed-case\">TET<\/jats:styled-content>2 and <jats:styled-content style=\"fixed-case\">TET<\/jats:styled-content>3 were comparable between both cell types. The expression levels of <jats:styled-content style=\"fixed-case\">DNMT<\/jats:styled-content>1 and <jats:styled-content style=\"fixed-case\">DNMT<\/jats:styled-content>3B <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> have a tendency to elevate in <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c fibroblasts. Among <jats:styled-content style=\"fixed-case\">TET<\/jats:styled-content> family members, the expression of <jats:styled-content style=\"fixed-case\">TET<\/jats:styled-content>1 was exclusively induced by hypoxia via <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101<jats:italic>\u03b1<\/jats:italic>\u2010independent pathways in <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c fibroblasts, but not in normal fibroblasts. The methylation level was decreased in <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c fibroblasts relative to normal fibroblasts, and 5hmC was present in dermal fibroblasts of skin sections from patients with <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c. <jats:styled-content style=\"fixed-case\">TET<\/jats:styled-content>1 expression in <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c fibroblasts was abnormally regulated in the hypoxic environment and accompanied by global <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> hypomethylation, suggesting the involvement of aberrant <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation in the pathogenesis of SSc.<\/jats:p>","DOI":"10.1111\/exd.12767","type":"journal-article","created":{"date-parts":[[2015,5,25]],"date-time":"2015-05-25T21:02:34Z","timestamp":1432587754000},"page":"841-846","source":"Crossref","is-referenced-by-count":53,"title":["Global <scp>DNA<\/scp> hypomethylation and hypoxia\u2010induced expression of the ten eleven translocation (<scp>TET<\/scp>) family, <scp>TET<\/scp>1, in scleroderma fibroblasts"],"prefix":"10.1111","volume":"24","author":[{"given":"Mai","family":"Hattori","sequence":"first","affiliation":[{"name":"Department of Dermatology Gunma University Graduate School of Medicine Maebashi Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Department of Dermatology Gunma University Graduate School of Medicine Maebashi Gunma 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