Department of Dermatology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China; Department of Dermatology and Venereology, School of Clinical Medicine, Guizhou Medical University, Guiyang, China.
Department of Dermatology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
J Invest Dermatol. 2022 Nov;142(11):3020-3029.e5. doi: 10.1016/j.jid.2022.04.022. Epub 2022 May 14.
OPN3, as a member of the opsin family, has various nonlight-dependent functions. Congenital melanocytic nevus (CMN) is a skin lesion with dark pigmentation that appears at birth and can be initiated by the BRAF mutation in melanocytes. However, the role of OPN3 in BRAF CMN cell melanogenesis has never been reported. In this study, we show that OPN3 acts as a negative regulator of melanin production by modulating BRAF signaling in BRAF CMN cells. Knocking down OPN3 expression can inhibit the BRAF/extracellular signal‒regulated kinase signaling pathway and upregulate the expression of microcephaly-related transcription factors, tyrosinase, and TRP1 and TRP2, thus increasing melanin levels in BRAF CMN cells. More remarkably, OPN3 and BRAF were found to form a physical complex. Furthermore, a three-dimensional nevus model was used to further prove the negative regulatory effect of OPN3 on BRAF CMN cell melanogenesis. Our study reveals a mechanism for OPN3-mediated melanogenesis in BRAF CMN cells, and these results may lead to a more personalized and economically viable approach to treating BRAF CMN.
OPN3 作为视蛋白家族的一员，具有多种非光依赖性功能。先天性黑素细胞痣（CMN）是一种出生时即出现色素沉着的皮肤病变，可由黑素细胞中的 BRAF 突变引发。然而，OPN3 在 BRAF CMN 细胞黑素生成中的作用尚未见报道。在本研究中，我们表明 OPN3 通过调节 BRAF CMN 细胞中的 BRAF 信号来充当黑色素生成的负调节剂。敲低 OPN3 表达可以抑制 BRAF/细胞外信号调节激酶信号通路，并上调小眼畸形相关转录因子、酪氨酸酶以及 TRP1 和 TRP2 的表达，从而增加 BRAF CMN 细胞中的黑色素水平。更显著的是，发现 OPN3 和 BRAF 形成物理复合物。此外，还使用三维痣模型进一步证明了 OPN3 对 BRAF CMN 细胞黑素生成的负调节作用。我们的研究揭示了 OPN3 介导的 BRAF CMN 细胞中黑色素生成的机制，这些结果可能为治疗 BRAF CMN 提供更个性化和经济可行的方法。
