microRNA-188在白癜风“黑素细胞经表皮脱失”中的作用及机制研究

miR-188, a kind of miRNA significantly increased in melanocyte of vitiligo with unkown function in pathogenesis of vitiligo was detected by miRNA array. Our study showed that Over-expression of miR-188 could lead to significant retraction of dendrite and faster retraction rate of dendriteand as well as low expression of β1 integrin of melanocytes, suggesting some relationship between miR-188 and the weaken adhesion of melanocyte, which is correlate to melanocytorrhagy, a hypothesis has been proposed in dermatology academe recently. Further study by.bioinformatics analysis and Luciferase reporter assay show that syntaxin 6 is a candidate target of miR-188. According to these results, we propose that the mechanism of miR-188 in melanocytorrhagy may be related to STX 6 by weaking adhesion of melanocyte thus induce leukasmus of vitiligo. To demonstrate this hypothesis, our study intends to collect more samples to investigate the clinical relevance of vitiligo and miR-188. In addition, to evaluate the function and mechanism of miR-188 in melanocytorrhagy through syntaxin 6. The study of miR-188.on melanocytorrhagy in vitiligo and its mechanism have not been reported. The implementation of this study may elucidate the regulatory mechanism, which will provide a theoretical basis for the targets of the treatment of vitiligo.

miR-188是我们通过miRNA芯片获得的、差异高表达于白癜风黑素细胞、在白癜风发病中功能未知的一个miRNA。实验发现miR-188过表达可导致黑素细胞树突明显回缩、变化速率显著增快、β1整合素表达下调，提示miR-188功能与黑素细胞粘附能力减弱有关，与近年学界提出的白癜风“黑素细胞经表皮脱失”学说相符；后续生物信息学分析和实验均证实syntaxin 6为其靶基因；据此，我们提出“miR-188通过抑制Syntaxin 6致黑素细胞经表皮脱失，进而参与白癜风白斑形成”的科学假说。为论证该假说，本研究拟进一步论证miR-188与白癜风白斑形成的相关性，并以syntaxin 6为机制线索，系统评价miR-188在白癜风黑素细胞经表皮脱失过程中的功能与机制。miR-188在白癜风黑素细胞经表皮脱失过程的作用与机制目前未见报道，因此本研究具有源头创新性，有望为白癜风防治提供新靶标。

白癜风是一种难治的色素脱失性疾病，发病机制不明。miR-188是我们通过miRNA芯片获得的、差异高表达于白癜风黑素细胞、在白癜风发病中的一个miRNA。实验发现miR-188过表达可导致黑素细胞树突明显回缩、变化速率显著增快、β1整合素表达下调，提示miR-188功能与黑素细胞黏附能力减弱有关，与近年学界提出的白癜风“黑素细胞经表皮脱失”学说相符；生物信息学分析和实验均证实syntaxin 6为其靶基因；据此，我们提出“miR-188通过抑制Syntaxin 6致黑素细胞经表皮脱失，进而参与白癜风白斑形成”的科学假说。为论证该假说，本研究进一步论证了miR-188与白癜风白斑形成的相关性，并以syntaxin 6为机制线索，系统评价miR-188在白癜风黑素细胞经表皮脱失过程中的功能与机制。研究结果发现miR-188高表达于白癜风患者黑素细胞，它通过抑制靶基因syntaxin 6下调黑素细胞整合素表达，降低细胞黏附力，使黑素细胞树突回缩经表皮脱失，进而参与白癜风白斑形成。本研究初步阐明miR-188在白癜风黑素细胞经表皮脱失过程的作用与机制，有望为白癜风防治提供新靶标。