CCN1/Cyr61 Stimulates Melanogenesis through Integrin α6β1, p38 MAPK, and ERK1/2 Signaling Pathways in Human Epidermal Melanocytes
CCN1/Cyr61 Stimulates Melanogenesis through Integrin α6β1, p38 MAPK, and ERK1/2 Signaling Pathways in Human Epidermal Melanocytes
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CCN1/Cyr61 通过整合素 alpha 6 beta 1、p38 MAPK 和 ERK1/2 信号通路刺激人表皮黑素细胞中的黑素生成
DOI：
10.1016/j.jid.2018.02.029
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发表时间：
2018
影响因子：
6.5
通讯作者：
Leihong Flora Xiang
中科院分区：
文献类型：
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作者：
Zhongyi Xu;Li Chen;Min Jiang;Qianqian Wang;Chengfeng Zhang;Leihong Flora Xiang
已知成纤维细胞衍生的黑色素生成旁分泌介质在黑色素形成中起作用。为了研究CCN1（也称为CYR61或富含半胱氨酸的61）对黑色素形成的影响，我们用重组CCN1蛋白处理正常人表皮黑色素细胞。我们的研究结果表明，CCN1通过整合素a6b1、p38 MAPK和ERK信号通路促进黑素小体成熟和上调MITF、TRP-1和酪氨酸酶来激活黑素形成。此外，我们发现UVB照射刺激正常人真皮成纤维细胞分泌CCN1，并且在成纤维细胞中敲低CCN1可减弱黑素细胞-成纤维细胞共培养系统中的黑色素生成。此外，通过免疫组织化学和免疫荧光染色，我们发现CCN1在太阳小痣和Riehl黑素病病变的真皮中都过表达。这些研究结果表明，CCN1是一种在UVB照射下分泌的成纤维细胞衍生的黑色素生成旁分泌介质，它可能在色素沉着症（如Riehl’s melanosis）的发生中发挥重要作用。
Fibroblast-derived melanogenic paracrine mediators are known to play a role in melanogenesis. To investigate the effect of CCN1 (also called CYR61 or cysteine-rich 61) on melanogenesis, normal human epidermal melanocytes were treated with recombinant CCN1 protein. Our findings show that CCN1 activates melanogenesis through promoting melanosome maturation and up-regulation of MITF, TRP-1, and tyrosinase via the integrin a6b1, p38 MAPK, and ERK signaling pathways. Furthermore, we found that UVB irradiation stimulates the secretion of CCN1 from normal human dermal fibroblasts, and CCN1 knockdown in fibroblasts attenuates melanogenesis in melanocyte-fibroblast co-culture system. Moreover, using immunohistochemistry and immunofluorescence staining, we discovered that CCN1 is overexpressed in the dermis of both solar lentigines and Riehl’s melanosis lesions. These findings suggest that CCN1 is a fibroblast-derived melanogenic paracrine mediator that is secreted under UVB irradiation, and it may play an important role in the development of hyperpigmentation diseases such as Riehl’s melanosis.