{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T19:59:54Z","timestamp":1776110394206,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T00:00:00Z","timestamp":1560902400000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Wnt\/\u03b2\u2010catenin signalling promotes melanogenesis in melanocytes and also induces melanocytogenesis from melanocyte stem cells (McSCs). Previous study reported that WNT1, a ligand which activates Wnt\/\u03b2\u2010catenin signalling pathway, was more highly expressed in the epidermis at SLs than in normal skin areas, suggesting that WNT1 causes hyperpigmentation. To elucidate the mechanism by which WNT1 expression is increased in SLs, we examined the methylation of 5\u2010carbon of cytosine (5mC), that is 5\u2010methylcytosine (5mC) level, in a region within the <jats:italic>WNT1<\/jats:italic> promoter; the methylation of the region was known to negatively regulate <jats:italic>WNT1<\/jats:italic> gene expression. We used an immortalized cell line of human interfollicular epidermal stem cells to analyse the effect of UVB irradiation on DNA methylation level of <jats:italic>WNT1<\/jats:italic> promoter and found that UVB irradiation caused demethylation of <jats:italic>WNT1<\/jats:italic> promoter and promoted <jats:italic>WNT1<\/jats:italic> mRNA expression. It was also found that UVB irradiation reduced the expression of DNA methyltransferase 1 (DNMT1), an enzyme responsible for maintaining methylation patterns during cell division. Pathological analysis of SLs and non\u2010SL regions in the human skin revealed that both DNMT1 expression and 5mC level were decreased at SLs compared to non\u2010SL skins. Furthermore, bisulphite sequencing showed that the methylated CpG level in <jats:italic>WNT1<\/jats:italic> promoter was also lower at SLs than in non\u2010SL skins. Thus, in the skin exposed to a high amount of UV rays, excessive expression of WNT1 is thought to be caused by the demethylation of <jats:italic>WNT1<\/jats:italic> promoter, and the upregulated WNT1 promotes melanocytogenesis and melanogenesis, then resulting in SL formation.<\/jats:p>","DOI":"10.1111\/exd.13949","type":"journal-article","created":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T09:48:11Z","timestamp":1556185691000},"page":"723-729","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["UV irradiation\u2010induced DNA hypomethylation around <i>WNT1<\/i> gene: Implications for solar lentigines"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7815-980X","authenticated-orcid":false,"given":"Takaaki","family":"Yamada","sequence":"first","affiliation":[{"name":"Research Laboratories Nippon Menard Cosmetic Co., Ltd. Nagoya Japan"},{"name":"Department of Applied Cell and Regenerative Medicine Fujita Health University School of Medicine Toyoake Japan"},{"name":"Department of Dermatology Fujita Health University School of Medicine Toyoake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiji","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Research Laboratories Nippon Menard Cosmetic Co., Ltd. Nagoya Japan"},{"name":"Department of Dermatology Fujita Health University School of Medicine Toyoake Japan"},{"name":"Nagoya University\u2010MENARD Collaborative Chair Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohei","family":"Iwata","sequence":"additional","affiliation":[{"name":"Department of Dermatology Fujita Health University School of Medicine Toyoake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaru","family":"Arima","sequence":"additional","affiliation":[{"name":"Department of Dermatology Fujita Health University School of Medicine Toyoake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsukane","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Dermatology Fujita Health University School of Medicine Toyoake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeki","family":"Numata","sequence":"additional","affiliation":[{"name":"Department of Dermatology Fujita Health University School of Medicine Toyoake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Nakata","sequence":"additional","affiliation":[{"name":"Research Laboratories Nippon Menard Cosmetic Co., Ltd. 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