常染色体显性遗传多囊肾病（autosomal dominant polycystic kidney disease, ADPKD）的发生发展与能量代谢水平密切相关，谷氨酰胺代谢在增殖的细胞中显著增强并为细胞提供能量ATP，但对于谷氨酰胺能量代谢与ADPKD发生发展之间的关系目前还没有研究报道。我们预实验结果发现，ADPKD肾脏细胞中谷氨酰胺代谢明显增强，且GLS1的表达和活性明显升高，GLS1抑制剂对ADPKD的发展有减缓作用。因此，我们提出假设：GLS1调控谷氨酰胺能量代谢异常是ADPKD发生发展的重要病理因素。本项目拟在分子、细胞与整体动物层面上，运用基因操纵和化学干预等方法，阐明GLS1表达升高的原因及其对ADPKD发生发展的调控作用；研究抑制GLS1功能活性通过下调ATP水平，影响ADPKD肾小管上皮细胞增殖和囊液分泌的具体机制，为开发ADPKD治疗药物提供新的靶点。

The development of ADPKD is closely related to the levels of energy metabolism. It has been shown that increased glutaminolysis in proliferating cells provides ATP, but the role of glutaminolysis in the development of ADPKD is unknown. Our preliminary data showed that glutaminolysis was obviously increased，and the expression of GLS1 was also upregulated in renal cells of ADPKD. Therefore, we predict that the abnormal expression of GLS1 induced ATP production from glutaminolysis is very important for ADPKD development. The aim of this project is to investigate the regulatory effects of GLS1 on the development of ADPKD by genetic techniques, chemical intervention and in vivo animal disease model. We will further explore how GLS1 inhibition downregulates ATP level and its impact on ADPKD renal tubular epithelial cell proliferation and fluid secretion, which will shed a light on new drug target development for ADPKD treatment.