Sahoo Anupama, Lee Bongyong, Boniface Katia, Seneschal Julien, Sahoo Sanjaya K, Seki Tatsuya, Wang Chunyan, Das Soumen, Han Xianlin, Steppie Michael, Seal Sudipta, Taieb Alain, Perera Ranjan J
Sanford Burnham Prebys Medical Discovery Institute, 6400 Sanger Road, Orlando, Florida, USA.
Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, Bordeaux, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1035, Biothérapies de Maladies Génétiques, Inflammatoires et Cancers (BMGIC), Immuno-dermatology ATIP-AVENIR, University of Bordeaux, Bordeaux, France.
J Invest Dermatol. 2017 Sep;137(9):1965-1974. doi: 10.1016/j.jid.2017.04.025. Epub 2017 May 11.
Vitiligo is a common chronic skin disorder characterized by loss of epidermal melanocytes and progressive depigmentation. Vitiligo has complex immune, genetic, environmental, and biochemical causes, but the exact molecular mechanisms of vitiligo development and progression, particularly those related to metabolic control, are poorly understood. In this study we characterized the human vitiligo cell line PIG3V and the normal human melanocyte line HEM-l by RNA sequencing, targeted metabolomics, and shotgun lipidomics. Melanocyte-enriched microRNA-211, a known metabolic switch in nonpigmented melanoma cells, was severely down-regulated in vitiligo cell line PIG3V and skin biopsy samples from vitiligo patients, whereas its predicted targets PPARGC1A, RRM2, and TAOK1 were reciprocally up-regulated. microRNA-211 binds to PGC1-α 3' untranslated region locus and represses it. Although mitochondrial numbers were constant, mitochondrial complexes I, II, and IV and respiratory responses were defective in vitiligo cells. Nanoparticle-coated microRNA-211 partially augmented the oxygen consumption rate in PIG3V cells. The lower oxygen consumption rate, changes in lipid and metabolite profiles, and increased reactive oxygen species production observed in vitiligo cells appear to be partly due to abnormal regulation of microRNA-211 and its target genes. These genes represent potential biomarkers and therapeutic targets in human vitiligo.
白癜风是一种常见的慢性皮肤疾病，其特征为表皮黑素细胞缺失和进行性色素脱失。白癜风具有复杂的免疫、遗传、环境和生化病因，但对白癜风发生和发展的确切分子机制，尤其是与代谢控制相关的机制了解甚少。在本研究中，我们通过RNA测序、靶向代谢组学和鸟枪法脂质组学对人白癜风细胞系PIG3V和正常人黑素细胞系HEM-1进行了特征分析。富含黑素细胞的微小RNA-211是无色素黑素瘤细胞中已知的代谢开关，在白癜风细胞系PIG3V和白癜风患者的皮肤活检样本中严重下调，而其预测靶点PPARGC1A、RRM2和TAOK1则上调。微小RNA-211与PGC1-α 3'非翻译区位点结合并抑制它。尽管线粒体数量恒定，但白癜风细胞中的线粒体复合物I、II和IV以及呼吸反应存在缺陷。纳米颗粒包被的微小RNA-211部分提高了PIG3V细胞的氧消耗率。白癜风细胞中观察到的较低氧消耗率、脂质和代谢物谱变化以及活性氧产生增加似乎部分归因于微小RNA-211及其靶基因的异常调控。这些基因代表了人类白癜风潜在的生物标志物和治疗靶点。
