黑素细胞对表皮渗透屏障功能的调节及机制研究

Increased pigmentation endows the epidermis of darkly pigmented subjects with enhanced barrier function, suggesting that melanocytes and/or melanin might be closely related to epidermal barrier function. The underlying mechanism of regulation of keratinocytes and epidermal barrier function by melanocytes is not clear. The keratinocytes-melanocytes cross-talk and associated-signals may play a critical role in this process. In this project, we will assess the epidermal permeability barrier of several melanocyte-associated skin diseases, and utilize a melanocyte-keratinocyte coculture system to identify and characterize genes in keratinocytes that are regulated by melanocytes and are involved in maintaining epidermal barrier function. Knockdown and overexpression of these genes will then be achieved using siRNA technology and Ady cDNA technology, respectively, to investigate the precise roles these genes play in maintaining epidermal barrier function. The results obtained will help us better understand the mechanisms underlying the interaction between keratinocytes and melanocytes, the regulation of epidermal barrier function by melanocytes, and the pathogenesis of melanocyte-related skin disorders, laying a theoretical foundation for the therapy of these diseases.

深肤色个体较浅肤色个体具有更优越的表皮屏障功能，提示黑素细胞和/或黑素与表皮渗透屏障功能密切相关。有关黑素细胞对角质形成细胞及对表皮渗透屏障功能影响的机制尚不清楚，黑素细胞-角质形成细胞的交叉对话及相关信号机制可能在该过程中起重要作用，本项目将进一步明确黑素细胞相关疾病的表皮渗透屏障功能，采用黑素细胞-角质形成细胞共培养体系，利用siRNA干扰技术和Ady cDNA技术分别抑制和过表达相关基因以观察其在维持人表皮屏障功能中的作用，籍此明确黑素细胞对表皮渗透屏障功能的具体调控机制，揭示黑素细胞和角质形成细胞之间的相互作用机制。本研究结果将有助于阐明与黑素细胞相关的皮肤病的发病机理，为临床治疗黑素失调相关性疾病打下基础。

深肤色个体较浅肤色个体具有更优越的表皮屏障功能，提示黑素细胞和/或黑素与表皮渗透屏障功能密切相关。有关黑素细胞对角质形成细胞及对表皮渗透功能的影响的机制尚不清楚。黑素细胞-角质形成细胞的交叉对话及相关信号机制可能在该过程中起重要作用。本项目检测了黑素细胞异常的相关疾病，如黑素细胞消失的典型代表的疾病白癜风发现，其表皮分化相关的蛋白caspase14、involucrin和loricrin的表达均低于正常人，且其脂蛋白相关的关键酶表达存在明显异常。我们在此基础上检测了不同肤色人群的表皮屏障功能，发现深肤色人群的角质形成细胞表达更高的表皮分化相关的蛋白，如caspase14、involucrin、loricrin和filaggrin,而凋亡相关的蛋白表达则无明显差异；采用黑素细胞-角质形成细胞共培养体系，发现人角质形成细胞在黑素细胞共培养后，其表皮分化相关蛋白caspase14表达显著上调，involucrin及loricrin的表达则增加并不明显。这些结果提示，黑素细胞/黑素减少的正常个体及黑素细胞功能及数目异常的患者均存在表皮分化蛋白的异常，这可能是不同肤色人群表皮屏障功能异常的生化基础，及伴黑素细胞功能及数目异常的疾病均伴有表皮渗透屏障功能异常及表皮分化蛋白的表达异常。