H19 RNA downregulation stimulated melanogenesis in melasma.
A variety of factors, including ultraviolet (UV) exposure, have been implicated in the pathogenesis of melasma. However, UV-induced hyperpigmentation usually recovers spontaneously, whereas melasma does not. Recently, we detected downregulation of the H19 gene on microarray analysis of hyperpigmented and normally pigmented skin from patients with melasma, and identified significant clinical correlations. The H19 downregulation was not accompanied by a reciprocal change of the imprinted gene, insulin-like growth factor II. Moreover, methylation pattern of the H19 promoter region in maternal ICR was variable. The H19 knockdown in melanocyte monoculture did not result in obvious tyrosinase overexpression, whereas the knockdown in a mixed cell culture system, composed of H19 siRNA transfected normal human keratinocytes and non-transfected normal human melanocytes, did induce not only a tyrosinase overexpression but also an increase of melanosome transfer. Estrogen treatment of the H19 RNA knockdown in the mixed cell culture was more than an additive effect on the tyrosinase overexpression, whereas UV irradiation was not. These findings suggest that downregulation of H19 and a sufficient dose of estrogen might be involved in the development of melasma.
Kim
Nan-Hyung
NH
Department of Dermatology, Dongguk University School of Medicine, Ilsandong-gu, Goyang-si, Gyenggi-do, South Korea. leeay@duih.org
Lee
Chang-Hoon
CH
Lee
Ai-Young
AY
D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation / Q000235:genetics; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000378:metabolism*; D008548:Melanosis / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D014442:Monophenol Monooxygenase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism*; D012727:Sex Characteristics; D012737:Sex Factors
D004967:Estrogens; C094335:H19 long non-coding RNA; D008543:Melanins; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; D014442:Monophenol Monooxygenase