自噬相关lncRNA-NONHSAT190308.1作为ceRNA在白癜风黑素细胞提前衰老中的作用和机制研究

In the recent years, melanocytorrhagy theory is another important mechanism of vitiligo following the theory of autoimmunity and melanocyte self-destruction. Melanocytes impairment and functional decline can lead to adhesion defects with peripheral keratinocytes and thus undergoing trans-epidermis loss.Comprehensive literatures showed that melanocytes around the skin lesions of patients with vitiligo show premature senescence and adhesion defects. Since premature senescence of melanocytes in vitiligo is closely related to autophagy. This study tends to establish a premature senescence model of human melanocytes induced by low concentration of H2O2 and use microarray technology to screen and predict autophagy associated lncRNA-NONHSAT190308.1 that acts as a ceRNA of miR-361-3p involved in the premature senescence process of melanocytes under oxidative stress. While studying the autophagy activity of the premature senescence melanocytes, the associated molecules with decreased autophagy activity were found in those melanocytes. We intend to study the role and mechanism of autophagy associated lncRNA-NONHSAT190308.1 in the melanocytorrhagy process of vitiligo in different molecular，cellular levels and in vitro tissue analogues, thus providing new ideas for the discovery of the pathogeny and treatment of vitiligo.

“黑素细胞（MC）经表皮脱失(melanocytorrhagy)”是近年来继自身免疫、黑素细胞自毁等理论后又一重要白癜风发病机制学说，即MC受损、功能衰退可导致其与周围角质形成细胞粘附缺陷而发生经表皮脱失。业已证实：白癜风皮损周围MC存在提前衰老，而此种衰老会直接导致其粘附减弱。由于白癜风MC提前衰老与自噬缺陷密切相关，本课题组通过体外建立低浓度过氧化氢诱导的人MC提前衰老模型，并采用基因芯片技术筛选并预测自噬相关lncRNA-NONHSAT190308.1作为ceRNA结合miR-361-3p调控氧化压力下MC的提前衰老进程；在研究白癜风与正常人提前衰老MC的自噬活动的同时，寻找出MC自噬活动减弱与其提前衰老的关联分子，以期在分子、细胞和组织模型等不同层面揭示自噬相关lncRNA-NONHSAT190308.1在白癜风MC发生经表皮脱失过程中的作用和机制，为该病病因及治疗研究提供新思路。

白癜风是一种皮肤科常见的色素脱失性疾病，以皮肤基底层的黑素细胞损坏丢失为特征。研究提示，白癜风患者白斑部位过氧化氢浓度明显增高，局部免疫组化示黑素细胞衰老相关标志物表达升高。本研究成功在体外建立了低浓度过氧化氢诱导的人黑素细胞的提前衰老模型，且检测了该情况下黑素细胞的黏附力、自噬及凋亡水平的变化。发现低浓度过氧化氢可导致黑素细胞的黏附力下降，自噬功能受损以及凋亡水平升高。通过对lncRNA、自噬、衰老相关标志物等的检测，发现氧化压力导致的黑素细胞提前衰老由MAPK通路介导，且该过程不依赖p53而依赖于p21途径发生。此外，积雪苷作为一种皮肤科常用药物，可以通过调节自噬对氧化压力下黑素细胞起到保护作用。综上，本研究明确了黑素细胞经表皮丢失现象与黑素细胞低浓度氧化压力下的提前衰老、自噬功能改变的相关性，且进一步探究了黑素细胞提前衰老的分子机制以及积雪苷对氧化压力下黑素细胞的保护作用机制。该项目执行结果主要反映在已发表或录用的论文25篇，获得专利1项，培养研究生2名，出版著作1本，主持课题3项。