lncRNA H19调控DP细胞毛囊诱导功能的机制研究

项目名称： lncRNA H19调控DP细胞毛囊诱导功能的机制研究

项目编号： No.81501685

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： 祝宁侠

作者单位： 汕头大学

项目金额： 18万元

中文摘要： 研究已证实低代毛乳头（DP）细胞可以诱导毛囊再生，高代则无此能力。我们知道，Wnt信号通路在DP细胞诱导毛囊再生中起关键作用。我们前期研究发现：低代DP细胞中和Wnt通路最密切相关的lncRNA H19表达水平明显升高，而WIF1表达水平则显著下调。最近研究显示，lncRNAs通过对WIF1的表观遗传学修饰调控Wnt信号通路。本课题组拟在此基础上，在细胞模型中采用RNA干扰/过表达、RT-PCR、RIP、ChIP等实验技术，明确lncRNA H19通过WIF1调控Wnt信号通路的分子机制，并进一步通过体内外毛囊诱导模型观察lncRNA H19对DP细胞毛囊诱导功能的影响，从而证实“lncRNA H19通过WIF1调控Wnt信号通路维持DP细胞诱导功能”的假说，其结果将为利用低/高代数DP细胞差异RNA的分析，开发恢复DP细胞诱导功能药物，治疗脱发性疾病提供新的思路。

中文关键词： 长链非编码RNA；毛乳头细胞；诱导功能；Wnt信号通路；H19

英文摘要： Early-passage dermal papilla (DP) cells have the ability to induce hair growth in vivo. However, the ability is lost on further culture. It is well-known Wnt signaling pathway plays crucial roles during hair-follicle induction ability. Our research found: lncRNA H19, most associated with Wnt signaling pathway, was significantly differentially expressed in DP4/DP10 cell groups. Moreover, WIF1 which is related to hair induction deregulation presented most remarkably differential expression. The recent research showed lncRNAs regulated Wnt/β-catenin signaling pathway by means of WIF1. Based on these results, first, we plan to induce high/low expression of lncRNA H19 in cultured DP cells to study its influence on Wnt signaling pathway. Second, RIP and ChIP with RNA pulldown are applied to detect the mechanism of lncRNA H19 in controlling WIF1 to regulate Wnt signaling pathway. Last, DP induction ability is observed in vivo and in vitro when regulating the expression of lncRNA H19. Therefore the results will demonstrate the hypothesis that lncRNA H19 plays an important role in maintaining DP cell induction ability by epigenetic modification of WIF1. This study will be beneficial to exploring drugs restoring the DP cell induction ability, and thus provides a new idea of treating hair loss.

英文关键词： lncRNA;dermal papilla cell;induction activity;Wnt signaling pathway;H19