Jiang Shan, Yu Xiuju, Dong Changsheng
a College of Animal Science and Veterinary Medicine , Shanxi Agricultural University , Taigu , China.
Biosci Biotechnol Biochem. 2016 Nov;80(11):2115-2121. doi: 10.1080/09168451.2016.1200455. Epub 2016 Jun 21.
Previously, we created miR-137 overexpressing transgenic mice that produced lighten color phenotypes including gray mice phenotype. However, the miR-137 functional role in coat color regulation is still not well understood. In this study, the quantity of melanin granule and the relative expression of TYRP2 in gray miR-137 overexpression transgenic mouse skin were significantly lower than that in C57BL/6J black mouse skin. The mRNA and protein expression level of c-Kit and c-Kit downstream gene Tyrp2 in miR-137 expression plasmid-transfected melanocytes were significantly down-regulated comparing with that of the control melanocytes. In melanocytes, miR-137 overexpression could decrease the enhanced expression of c-Kit and Tyrp2 and the increased melanin production caused by UV treatment. The target relationship of miR-137 and c-Kit was identified by luciferase assay. The results suggest that miR-137 could inhibit melanogenesis in mouse skin melanocytes by repressing the expression of c-Kit and Tyrp2 in SCF/c-Kit signaling pathway.
此前，我们构建了过表达miR-137的转基因小鼠，其表现出毛色变浅的表型，包括灰色小鼠表型。然而，miR-137在毛色调控中的功能作用仍未完全明确。在本研究中，灰色miR-137过表达转基因小鼠皮肤中黑色素颗粒的数量以及TYRP2的相对表达量均显著低于C57BL/6J黑色小鼠皮肤。与对照黑素细胞相比，miR-137表达质粒转染的黑素细胞中c-Kit及其下游基因Tyrp2的mRNA和蛋白表达水平均显著下调。在黑素细胞中，过表达miR-137可降低紫外线处理导致的c-Kit和Tyrp2表达增强以及黑色素生成增加。通过荧光素酶报告基因实验鉴定了miR-137与c-Kit的靶向关系。结果表明，miR-137可通过抑制SCF/c-Kit信号通路中c-Kit和Tyrp2的表达来抑制小鼠皮肤黑素细胞中的黑色素生成。
