TGFβ2 Upregulates Tyrosinase Activity through Opsin-3 in Human Skin Melanocytes In Vitro
TGFβ2 Upregulates Tyrosinase Activity through Opsin-3 in Human Skin Melanocytes In Vitro
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DOI：
10.1016/j.jid.2021.01.040
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发表时间：
2021-10-20
影响因子：
6.5
通讯作者：
Lu, Hongguang
中科院分区：
文献类型：
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作者：
Wang, Yu;Lan, Yinghua;Lu, Hongguang
视蛋白-3（Opsin-3，OPN 3）是人类黑素细胞黑素生成的潜在关键调节因子。OPN 3介导的黑素细胞黑素生成调节是如何触发的在很大程度上尚不清楚。TGF β可以抑制人黑素细胞的生长，减少黑素细胞中黑色素的合成。然而，TGF β 2是否可以通过OPN 3调节正常人原代黑素细胞中的色素沉着是完全未知的。在这项研究中，我们建立了一个与人表皮黑素细胞和角质形成细胞共培养模型。与单独培养的细胞相比，共培养的细胞中OPN 3、酪氨酸酶（TYR）、酪氨酸酶相关蛋白（TRP）-1和TRP-2的表达和TYR活性均升高。此外，在与角质形成细胞共培养的黑素细胞的培养上清液中检测到TGF β 2水平升高。黑素细胞中的OPN 3抑制降低了TYR、TRP-1和TRP-2的表达并下调了TYR活性。我们的研究结果表明，TGF β 2通过OPN 3和下游钙依赖性G蛋白偶联信号通路上调人黑素细胞中TYR活性和TRP-1和TRP-2表达，以诱导黑素生成。有趣的是，用TGF β 2受体抑制剂LY 2109761（10 mM）处理不通过OPN 3抑制TGF β 2诱导的黑素细胞黑素生成。总的来说，我们的数据表明，TGF β 2通过OPN 3通过TGF β 2受体独立和钙依赖性G蛋白偶联信号通路上调TYR活性。
Opsin-3 (OPN3) is a potential key regulator of human melanocyte melanogenesis. How OPN3-mediated regulation of melanocyte melanogenesis is triggered is largely unclear. TGF beta can inhibit the growth of human melanocytes and reduce melanin synthesis in melanocytes. However, whether TGF beta 2 can modulate pigmentation in normal human primary melanocytes through OPN3 is entirely unknown. In this study, we constructed a coculture model with human epidermal melanocytes and keratinocytes. OPN3, tyrosinase (TYR), tyrosinase-related protein (TRP)-1, and TRP-2 expression and TYR activity were detected to be higher in cocultured cells than in monocultured cells. Moreover, elevated levels of TGF beta 2 were detected in the culture supernatant of melanocytes cocultured with keratinocytes. OPN3 inhibition in melanocytes decreased TYR, TRP-1, and TRP-2 expression and downregulated TYR activity. Our findings indicate that TGF beta 2 upregulates TYR activity and TRP-1 and TRP-2 expression in human melanocytes through OPN3 and downstream calcium-dependent G-protein coupled signaling pathways to induce melanogenesis. Interestingly, treatment with the TGF beta 2 receptor inhibitor LY2109761 (10 mM) did not inhibit TGF beta 2-induced melanocyte melanogenesis though OPN3. Collectively, our data suggest that TGF beta 2 upregulates TYR activity through OPN3 through a TGF beta 2 receptoreindependent and calcium-dependent G-protein coupled signaling pathway.