Li Dong, Zhou Ting, She Qiuyun, Nie Xiaoqi, Liu Zhong, Pan Ronghua, Wei Yujia, Deng Yunhua
Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Invest Dermatol. 2022 Dec;142(12):3262-3273.e11. doi: 10.1016/j.jid.2022.05.1086. Epub 2022 Jun 9.
Circulating exosomal microRNAs have been used as potential biomarkers for various disorders. However, to date, the microRNA expression profile of circulating exosomes in patients with segmental vitiligo (SV) has not been identified. Thus, we aimed to identify the expression profile of circulating exosomal microRNAs and investigate their role in the pathogenesis of SV. Our study identified the expression profile of circulating exosomal microRNAs in SV and selected miR-493-3p as a candidate biomarker whose expression is significantly increased in circulating exosomes and perilesions in patients with SV. Circulating exosomes were internalized by human primary keratinocytes and increased dopamine secretion in vitro. Furthermore, miR-493-3p overexpression in keratinocytes increased dopamine concentration in the culture supernatant, which led to a significant increase in ROS and melanocyte apoptosis as well as a decrease in melanocyte proliferation and melanin synthesis in the coculture system by targeting HNRNPU. We also confirmed that HNRNPU could bind to and regulate COMT, a major degradative enzyme of dopamine. Hence, circulating exosomal miR-493-3p is a biomarker for SV, and the miR-493-3p/HNRNPU/COMT/dopamine axis may contribute to melanocyte dysregulation in the pathogenesis of SV.
循环外泌体微小RNA已被用作多种疾病的潜在生物标志物。然而，迄今为止，节段性白癜风（SV）患者循环外泌体的微小RNA表达谱尚未明确。因此，我们旨在确定循环外泌体微小RNA的表达谱，并研究它们在SV发病机制中的作用。我们的研究确定了SV中循环外泌体微小RNA的表达谱，并选择miR-493-3p作为候选生物标志物，其在SV患者的循环外泌体和皮损周围组织中的表达显著增加。循环外泌体被人原代角质形成细胞内化，并在体外增加多巴胺分泌。此外，角质形成细胞中miR-493-3p的过表达增加了培养上清液中的多巴胺浓度，通过靶向HNRNPU导致共培养系统中活性氧显著增加、黑素细胞凋亡增加以及黑素细胞增殖和黑色素合成减少。我们还证实HNRNPU可以结合并调节COMT，COMT是多巴胺的一种主要降解酶。因此，循环外泌体miR-493-3p是SV的生物标志物，miR-493-3p/HNRNPU/COMT/多巴胺轴可能在SV发病机制中导致黑素细胞失调。
