钙结合蛋白S100A6介导的Wnt信号通路在常染色体显性多囊肾病进展中的机制研究

ADPKD (Autosomal Dominant Polycystic Kidney Disease) is the most common hereditary kidney disease. Researches involved in ADPKD mainly focus on the progress from genetic mutation to cyst formation, which remains to be a large difficulty. Thus to explore the molecular mechanism of cyst formation has great significance on clinical surveillance and treatment. In our previous studies, a calcium binding protein S100A6 shows higher expression level in the early stage of ADPKD mice kidney tissues. More importantly, the increased expression of S100A6 was observed even before the appearance of kidney cysts, which is likely mediated by Wnt signaling. Therefore, we speculate that S100A6 participates in the cyst formation of ADPKD from early stage mediated by Wnt signaling. This project plans to explore the role and underlying mechanism of S100A6 in the progress of ADPKD as well as its relationship with Wnt signaling. The techniques we intend to use involving cell lines, ADPKD mice model, bioinformatics tools, biological function experiments, Co-Ip, etc. The successful completion of this project will complement the mechanism of cyst formation in ADPKD and provide a new strategy for early surveillance and treatment of ADPKD.

常染色体显性多囊肾（ADPKD）是最常见的遗传性肾脏疾病，从致病基因突变到囊肿形成过程的机制研究是ADPKD相关研究的重点与难点，对该疾病的早期监测及干预有着重大临床意义。我们在前期研究中发现钙结合蛋白S100A6在ADPKD小鼠疾病模型的早期即存在高水平表达。更重要的是，S100A6的蛋白表达在肾脏囊肿形成之前就已经呈现升高，并且极有可能通过Wnt信号通路而发挥其生物学作用。因此推测，S100A6通过Wnt信号通路的介导而参与了ADPKD早期的囊肿形成过程。本项目拟通过体外细胞株构建、ADPKD小鼠疾病模型、生物信息学、生物功能实验、免疫共沉淀等技术探究S100A6在囊肿形成过程中的生物学作用，并验证其与Wnt信号通路间关系。本项目的成功实施将为ADPKD的囊肿形成机制作一补充，为疾病的早期监测与干预提供新的策略。

常染色体显性多囊肾病(Autosomal Dominant Polycystic Kidney Disease, ADPKD) 是最常见的遗传性肾脏疾病。其主要表现为多发双侧肾脏的囊性病变，并最终将进展至尿毒症阶段。该疾病目前的治疗方法并不能够阻止疾病进展的进程，因此早期干预疾病的发展对延缓患者肾功能减退有着重要的意义。本课题研究通过体外细胞株构建、ADPKD小鼠疾病模型、生物信息学、生物学功能实验等揭示了在ADPKD疾病早期，钙结合蛋白S100A6的表达即出现升高，这一升高表达一直延续至疾病中后期，其过表达与加快细胞增殖相关，并与Wnt/β-catenin信号通路的高表达存在关联。该发现为ADPKD的早期筛查及疾病早期干预提供了新的思路，并为临床转化提供支持。