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However, whether <jats:styled-content style=\"fixed-case\">ANGPTL<\/jats:styled-content>2 functions in melanin production remains unclear. To assess this possibility, we overexpressed <jats:italic>Angptl2 in<\/jats:italic> the melanoma line B16 and in the keratinocyte line HaCaT. Relative to controls, <jats:italic>Angptl2<\/jats:italic>\u2010expressing B16 cells produced higher melanin levels via tyrosinase induction. Accordingly, <jats:italic>Angptl2<\/jats:italic>\u2010expressing HaCaT cells secreted relatively high levels of both endothelin\u20101 (<jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101) and \u03b1\u2010melanocyte\u2010stimulating hormone (\u03b1\u2010<jats:styled-content style=\"fixed-case\">MSH<\/jats:styled-content>). Moreover, treatment with an extract from <jats:italic>Chrysanthemum indicum<\/jats:italic>\u00a0\u00d7\u00a0<jats:italic>Erigeron annuus<\/jats:italic> (<jats:styled-content style=\"fixed-case\">CE<\/jats:styled-content>) suppressed <jats:styled-content style=\"fixed-case\">ANGPTL<\/jats:styled-content>2 expression and repressed tyrosinase induction in melanocytes and of \u03b1\u2010<jats:styled-content style=\"fixed-case\">MSH<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101 in keratinocytes. Our data suggest that <jats:styled-content style=\"fixed-case\">ANGPTL<\/jats:styled-content>2 expression in keratinocytes and melanin\u2010producing cells accelerates pigment production and that treatment of skin with a <jats:styled-content style=\"fixed-case\">CE<\/jats:styled-content> extract could prevent melanin accumulation.<\/jats:p>","DOI":"10.1111\/exd.13862","type":"journal-article","created":{"date-parts":[[2018,12,16]],"date-time":"2018-12-16T11:05:20Z","timestamp":1544958320000},"page":"152-160","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["UV\u2010B\u2010activated B16 melanoma cells or HaCaT keratinocytes accelerate signaling pathways associated with melanogenesis via ANGPTL 2 induction, an activity antagonized by Chrysanthemum extract"],"prefix":"10.1111","volume":"28","author":[{"given":"Gaku","family":"Satou","sequence":"first","affiliation":[{"name":"Saishunkan Pharmaceutical Co. 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