黑素细胞分泌sPmel17驱动对UVB诱导白癜风复色表皮微环境的调节

尽管临床证实用NB-UVB或308nm准分子光照射治疗白癜风有效，但目前对这类光疗诱导白癜风复色的细胞与分子机制并不十分清楚。而且，光疗通常起效慢，个体间的疗效差异较大，亟待找到一种药物（或方法）能加速UVB诱导白癜风复色。实质上，白癜风复色是指一群被激活的黑素细胞（MC）向角质形成细胞（KC）中迁移并增殖的过程。我们推测UVB照射可能刺激MC分泌sPmel17蛋白，活化sPmel17-FHL2-TGFbeta1分子通路，调节有利于白癜风复色的表皮微环境。本项目拟用MC和KC共培养模型以及荷载人白癜风皮肤异种移植物裸鼠模型，在体内（动物水平）和体外（细胞水平）观察针对sPmel17、FHL2、TGFbeta1靶点的特异性抑制剂或基因沉默干预对MC/KC成熟、分化、移行和灶性粘附结构的影响。本课题对认识MC驱动的对KC和表皮微环境调节机制以及探讨白癜风治疗新药物都有着重大意义。

Despite clinical evidence that indicates the effectiveness of phototherapy using narrowband ultraviolet B (NB-UVB) or 308nm excimer light radiation in the treatment of vitiligo, there is very little known about their mechanisms of action at the cellular and molecular levels. However, the responses of vitiligo to these phototherapies are very delayed and also differ greatly from one another. It is urgent to develop a new medication or method for accelerating UVB-induced repigmentation in the patients with vitiligo. Actually, the repigmentation represents the migration and proliferation of activated melanocytes (MC) into the keratinocyte (KC) population in the skin, we assume that MCs likely produce a secreted form of Pmel17 protein (sPmel17) upon exposure to UVB radiation, whereby stimulates the sPmel17-FHL2-TGFbeta1 pathway and promotes an epidermal microenvironment supportive for vitiligo repigmentation. In this study, we are planning to examine the changes of molecular markers specific for maturation, differentiation, migration, and focal adhesion of MCs or/ KCs both in the cocultured cell model (in vitro) and the mouse model grafted with human vitiligo skin tissue (in vivo), while being treated or untreated by the specific inhibitor or gene silencing for sPmel17, FHL2, and TGFbeta1. Our study proposed herein is of great significance to understand the MC-driven regulation(s) for KCs and epidermal milieu, even developing a novel therapeutic for vitiligo.