神经激肽1受体与内皮素B受体间cross-talk对黑素体形成与转运的影响及相关机制研究

项目名称： 神经激肽1受体与内皮素B受体间cross-talk对黑素体形成与转运的影响及相关机制研究

项目编号： No.81503176

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 周佳

作者单位： 中国药科大学

项目金额： 17.9万元

中文摘要： 对黑素细胞的研究在美容化妆品领域及医学领域均有重要意义，黑素体形成与转运是目前黑素细胞功能研究的热点及难点。我们前期研究发现，P物质（SP）参与黑色素合成过程，其受体NK-1R在此过程中发挥不可或缺的作用。最新研究报导，内皮素-1（ET-1）及其受体ETBR也参与调节黑素细胞功能，影响黑色素合成及黑素体的形成和分布，而SP通过NK-1R上调内源性ET-1含量及ETBR表达。由于NK-1R与ETBR均属于G蛋白偶联受体（GPCRs），鉴于GPCRs之间可以通过β-抑制蛋白（β-arrestin）介导的过程发生同源性或异源性的调控，本研究旨在研究NK-1R与ETBR间cross-talk以及该种联系对黑素体形成和分布的影响。拟以人源黑素细胞及3D重组人造皮肤模型为研究材料，运用分子生物学相关方法、免疫组织化学法、细胞免疫荧光法、扫描/透射电镜法、小RNA干扰技术、临位连接技术等阐明相关机制。

中文关键词： 神经激肽1受体；内皮素B受体；；cross-talk；黑素体形成与转运；分子机制

英文摘要： It is of great research significance on melanocyte functions for both cosmetics and medicine field. At present, study of melanosome formation and transport is still the hotspot and difficulty. Our initial findings showed that substance P (SP) took part in melanogenesis and its receptor NK-1R played an indispensable role. Recently, it is reported that endthelin-1 (ET-1) and its receptor ETBR also participate in regulating melanocyte functions, making impact on melanin biosynthesis, melanosome formation and transport. Above all, SP increases endogenous ET-1 content and up-regulates ETBR expression. Both NK-1R and ETBR belong to G-protein-coupled receptors super family (GPCRs). Considering the homologous or heterologous controls mediated by β-arrestin among members of GPCRs, the present research is designed to study the cross-talk between NK-1R and ETBR, and the effect of this cross-talk on melanosome formation and transport. In this research project, we use normal human foreskin-derived epidermal melanocytes and 3D artificial skin model as the research materials, applying molecular biology methods (WB, Protein Array), immunohistochemical method (ICH), cell immunofluorescence method (cIF), scanning/transmission electron microscopy (STEM), small RNA interference (siRNA) and proximity ligation assay (PLA) to elucidate mechanisms.

英文关键词： Neurokinin receptor 1;endthelin receptor B;cross-talk;melanosome formation and transport;molecular mechanism