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Circulating Exosomal miR-493-3p Affects Melanocyte Survival and Function by Regulating Epidermal Dopamine Concentration in Segmental Vitiligo

  • Author Footnotes
    2 These authors contributed equally to this work.
    Dong Li
    Footnotes
    2 These authors contributed equally to this work.
    Affiliations
    Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Author Footnotes
    2 These authors contributed equally to this work.
    Ting Zhou
    Footnotes
    2 These authors contributed equally to this work.
    Affiliations
    Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Qiuyun She
    Affiliations
    Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Xiaoqi Nie
    Affiliations
    Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Zhong Liu
    Affiliations
    Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Ronghua Pan
    Affiliations
    Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Yujia Wei
    Affiliations
    Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Yunhua Deng
    Correspondence
    Correspondence: Yunhua Deng, Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.
    Affiliations
    Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Author Footnotes
    2 These authors contributed equally to this work.
      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.

      Abbreviations:

      KC (keratinocyte), LC-MS (liquid chromatography-mass spectrometry), miRNA (microRNA), NHEK (normal human epidermal keratinocyte), NHEM (normal human epidermal melanocyte), NSV (nonsegmental vitiligo), RIP (RNA immunoprecipitation), SV (segmental vitiligo)
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