College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, China.
College of Animal Science and Veterinary Medicine, Jiangxi Agricultural University, Nanchang, China.
Exp Dermatol. 2020 May;29(5):467-476. doi: 10.1111/exd.14095. Epub 2020 Apr 2.
Melanogenesis, migration and proliferation of melanocytes are important factors that determine the hair colours of mammals. MicroRNAs (miRNAs) have been shown to be closely related to these processes. In melanocytes of alpacas, insulin-like growth factor 1 (IGF1) has been shown to improve melanogenesis through the cyclic AMP (cAMP) pathway. miR-379 was predicted to target insulin-like growth factor (IGF) receptor 1 (IGF1R), which binds to IGF1. Therefore, we hypothesized that miR-379 could mediate melanogenesis, migration and proliferation of melanocytes. Here, we report that miR-379 was highly expressed in alpaca melanocytes. Subsequent overexpression of miR-379 in alpaca melanocytes led to the generation of the phenotype of melanogenesis, proliferation and migration. In addition, the expression of genes related to these phenotypes in melanocytes was detected. Our results showed that miR-379 targets IGF1R in melanocytes. The overexpression of miR-379 stimulated dendrite extension or elongation and limited the perinuclear distribution of melanin, but inhibited melanogenesis via cAMP response element (CRE)-binding protein (CREB)/microphthalmia-associated transcription factor (MITF) pathway. miR-379 attenuated melanocyte migration by downregulating the focal adhesion kinase (FAK) and enhanced melanocyte proliferation by upregulating protein kinase B (AKT). These observations suggest the involvement of miR-379 in the physiological regulation of melanocytes, mediated by targeting IGF1R on insulin receptor (IR) compensation and subsequent crosstalk.
黑色素生成、黑素细胞的迁移和增殖是决定哺乳动物毛发颜色的重要因素。研究表明,微小 RNA(miRNA)与这些过程密切相关。在羊驼的黑素细胞中,胰岛素样生长因子 1(IGF1)已被证明通过环腺苷酸(cAMP)途径改善黑色素生成。miR-379 被预测靶向胰岛素样生长因子(IGF)受体 1(IGF1R),后者与 IGF1 结合。因此,我们假设 miR-379 可以介导黑素细胞的黑色素生成、迁移和增殖。在这里,我们报告 miR-379 在羊驼黑素细胞中高度表达。随后在羊驼黑素细胞中过表达 miR-379 导致黑色素生成、增殖和迁移的表型产生。此外,还检测了与这些表型相关的基因在黑素细胞中的表达。我们的结果表明,miR-379 在黑素细胞中靶向 IGF1R。miR-379 的过表达刺激树突延伸或伸长,并限制黑色素的核周分布,但通过 cAMP 反应元件(CRE)结合蛋白(CREB)/小眼畸形相关转录因子(MITF)途径抑制黑色素生成。miR-379 通过下调粘着斑激酶(FAK)抑制黑素细胞迁移,并通过上调蛋白激酶 B(AKT)增强黑素细胞增殖。这些观察结果表明,miR-379 通过靶向 IGF1R 介导胰岛素受体(IR)代偿和随后的串扰,参与黑素细胞的生理调节。