Guanine Deaminase in Human Epidermal Keratinocytes Contributes to Skin Pigmentation
Guanine Deaminase in Human Epidermal Keratinocytes Contributes to Skin Pigmentation
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DOI：
10.3390/molecules25112637
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发表时间：
2020-06-01
期刊：
影响因子：
4.6
通讯作者：
Chang, Sung Eun
中科院分区：
文献类型：
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作者：
Jung, Joon Min;Noh, Tai Kyung;Chang, Sung Eun
表皮角质形成细胞被认为是调节黑素生成的最重要的邻近细胞。我们以前的研究使用微阵列显示，鸟嘌呤脱氨酶（GDA）基因表达在黄褐斑病变高度增加。因此，我们研究了GDA在皮肤色素沉着中的作用。我们检测了诊断为Riehl黑变病的炎症后色素沉着过度（PIH）病变中的GDA表达。我们通过定量PCR、免疫荧光染色、基于小干扰RNA的GDA敲低和腺病毒介导的GDA过表达进一步研究了角质形成细胞来源的GDA在黑素生成中的可能作用。我们发现高色素病变表皮中的GDA阳性率高于病变周围表皮。UVB照射和干细胞因子（SCF）加内皮素-1（ET-1），这是众所周知的促黑素生成刺激上调GDA的表达在角质形成细胞单独培养和角质形成细胞和黑素细胞共培养。GDA敲低下调黑素含量，而GDA过表达促进黑素合成的共培养。当黑素细胞用UVB暴露的角质形成细胞条件培养基处理时，黑素含量增加。此外，GDA敲低降低角质形成细胞中SCF和ET-1的表达水平。表皮角质形成细胞中的GDA可能通过上调SCF和ET-1促进黑素生成，提示其在皮肤色素过度性疾病中的作用。
Epidermal keratinocytes are considered as the most important neighboring cells that modify melanogenesis. Our previous study used microarray to show that guanine deaminase (GDA) gene expression is highly increased in melasma lesions. Hence, we investigated the role of GDA in skin pigmentation. We examined GDA expression in post-inflammatory hyperpigmentation (PIH) lesions, diagnosed as Riehl's melanosis. We further investigated the possible role of keratinocyte-derived GDA in melanogenesis by quantitative PCR, immunofluorescence staining, small interfering RNA-based GDA knockdown, and adenovirus-mediated GDA overexpression. We found higher GDA positivity in the hyperpigmentary lesional epidermis than in the perilesional epidermis. Both UVB irradiation and stem cell factor (SCF) plus endothelin-1 (ET-1) were used, which are well-known melanogenic stimuli upregulating GDA expression in both keratinocyte culture alone and keratinocyte and melanocyte coculture. GDA knockdown downregulated melanin content, while GDA overexpression promoted melanogenesis in the coculture. When melanocytes were treated with UVB-exposed keratinocyte-conditioned media, the melanin content was increased. Also, GDA knockdown lowered SCF and ET-1 expression levels in keratinocytes. GDA in epidermal keratinocytes may promote melanogenesis by upregulating SCF and ET-1, suggesting its role in skin hyperpigmentary disorders.