Laboratory of Comparative Physiology of Pigmentation, Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo 05508-090, Brazil.
DNA Repair Lab, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.
Curr Issues Mol Biol. 2021 Oct 4;43(3):1436-1450. doi: 10.3390/cimb43030101.
Skin melanocytes harbor a complex photosensitive system comprised of opsins, which were shown, in recent years, to display light- and thermo-independent functions. Based on this premise, we investigated whether melanopsin, OPN4, displays such a role in normal melanocytes. In this study, we found that murine melanocytes displayed a faster proliferation rate compared to melanocytes. Cell cycle population analysis demonstrated that OPN4 melanocytes exhibited a faster cell cycle progression with reduced G-G and highly increased S and slightly increased G/M cell populations compared to the counterparts. Expression of specific cell cycle-related genes in melanocytes exhibited alterations that corroborate a faster cell cycle progression. We also found significant modification in gene and protein expression levels of important regulators of melanocyte physiology. PER1 protein level was higher while BMAL1 and REV-ERBα decreased in melanocytes compared to cells. Interestingly, the gene expression of microphthalmia-associated transcription factor (MITF) was upregulated in melanocytes, which is in line with a higher proliferative capability. Taken altogether, we demonstrated that OPN4 regulates cell proliferation, cell cycle, and affects the expression of several important factors of the melanocyte physiology; thus, arguing for a putative tumor suppression role in melanocytes.
皮肤黑素细胞内存在一个复杂的感光系统，其中包含视蛋白，近年来的研究表明，视蛋白具有光和热非依赖性的功能。基于这一前提，我们研究了黑素视蛋白（OPN4）是否在正常黑素细胞中具有这种作用。在这项研究中，我们发现与 黑素细胞相比，鼠黑素细胞表现出更快的增殖速度。细胞周期群体分析表明，与 黑素细胞相比，OPN4 黑素细胞的细胞周期进展更快，G-G 期减少，S 期和 G/M 期略有增加。黑素细胞中特定细胞周期相关基因的表达发生改变，这与更快的细胞周期进程相吻合。我们还发现，黑素细胞中重要的黑素细胞生理调节因子的基因和蛋白表达水平发生了显著改变。与 细胞相比，PER1 蛋白水平升高，而 BMAL1 和 REV-ERBα 降低。有趣的是，与 细胞相比，小眼畸形相关转录因子（MITF）的基因表达上调，这与更高的增殖能力一致。总的来说，我们证明了 OPN4 调节细胞增殖、细胞周期，并影响黑素细胞生理的几个重要因子的表达；因此，OPN4 在黑素细胞中可能具有肿瘤抑制作用。
