Department of Dermatology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, 430060, China.
Department of Dermatology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, No. 100 Hongkong Road, Wuhan, 430015, China.
Exp Cell Res. 2019 Nov 1;384(1):111615. doi: 10.1016/j.yexcr.2019.111615. Epub 2019 Sep 6.
The decreased adhesion ability of melanocytes to the neighboring keratinocytes prompts melanocytes to lose from the epidermis, comprising the critical step in vitiligo pathogenesis. The repigmentation process involves the migration of melanocytes to the lesional area. This study aims to investigate the role and mechanism of microRNA (miR)-9 in the adhesion and migration of melanocytes during vitiligo repigmentation induced by UVB treatment. The HaCaT keratinocytes were used to mimic lesional condition and the PIG1 melanocytes as perilesional condition. Human lesional vitiligo specimens showed increased miR-9 and decreased adhesion molecules such as E-cadherin and β1 integrin. Furthermore, UVB exposure upregulated IL-10, E-cadherin, and β1 integrin, downregulated miR-9 in HaCaT cells. Moreover, the increased IL-10 by UVB exposure decreased miR-9 level by inducing miR-9 methylation via methyltransferase DNMT3A in HaCaT cells. Additionally, miR-9 targeted and inhibited E-cadherin and β1 integrin in HaCaT cells, and suppressed migration of PIG1 cells to UVB-exposed HaCaT cells. In conclusion, miR-9 was suppressed by IL-10 and inhibited migration of PIG1 cells to HaCaT cells during UVB-mediated vitiligo repigmentation.
黑素细胞与邻近角质形成细胞的黏附能力降低,促使黑素细胞从表皮脱落,这是白癜风发病机制中的关键步骤。复色过程涉及黑素细胞向病变区域的迁移。本研究旨在探讨 microRNA(miR)-9 在 UVB 诱导的白癜风复色过程中对黑素细胞黏附和迁移的作用及其机制。使用 HaCaT 角质形成细胞模拟病变条件,PIG1 黑素细胞作为病变周围条件。人类病变性白癜风标本显示 miR-9 增加,黏附分子如 E-钙黏蛋白和β1 整合素减少。此外,UVB 暴露上调 HaCaT 细胞中的 IL-10、E-钙黏蛋白和β1 整合素,下调 miR-9。此外,UVB 暴露通过诱导甲基转移酶 DNMT3A 增加 HaCaT 细胞中的 IL-10,从而降低 miR-9 水平。此外,miR-9 靶向并抑制 HaCaT 细胞中的 E-钙黏蛋白和β1 整合素,并抑制 PIG1 细胞向 UVB 暴露的 HaCaT 细胞迁移。总之,在 UVB 介导的白癜风复色过程中,IL-10 抑制了 miR-9 的表达,并抑制了 PIG1 细胞向 HaCaT 细胞的迁移。