哺乳动物雷帕霉素靶蛋白复合物1(mTORC1)是接受细胞内外信号调节细胞生长与代谢的中心分子，但它在钾代谢调节中的作用与机制尚未见报道。课题组前期实验中构建了集合管上皮主细胞特异性敲除Tsc1基因的小鼠（mTORC1过度激活），发现该小鼠出现高钾血症致死，且mTORC1可负调节集合管细胞内调控钾分泌的关键激酶SGK1（Serum and Glucocorticoid inducible kinase 1），提示mTORC1可能通过SGK1调节集合管泌钾功能。本项目拟通过集合管主细胞特异性敲除Tsc1(mTORC1过度激活)、Raptor（mTORC1被抑制)基因的小鼠以及敲除这些基因的集合管上皮细胞、离体集合管等模型，研究mTORC1调节SGK1及肾脏集合管泌钾功能的作用及其分子机制，为钾代谢调节机制及mTORC1的功能研究增加新内容，为集合管功能障碍引起钾代谢失调的疾病防治提供新靶点。

Mammallian target of rapamycin complex 1(mTORC1) plays a central role in regulating cell growth and metabolism by integrating a variety of extra- and intra-cellular signals. However, its roles and mechanisms in regulation of potassium hemosis are still unknown. Our preliminary data show that specific deletion of Tsc1 in the priciple cell of the collecting duct using the cre-loxp technique resulted in hyperkaliemia and death of the mice about eight weeks after birth.Meanwhile, serum- and glucocorticoid- inducible kinase 1,a key regulator of potassium excretion in the collecting duct cell decreased dramatically.It is suggested that mTORC1 could regulate the patassium excretion of renal collecting duct via SGK1.Using the pricipal cell of the renal collecting duct -specific deletion of Tsc1 (mTORC1 overactivation), Raptor (inhibition of mTORC1) and primary collecting duct cell，collecting duct cell line M-1 as cellular and animal models, this project aims to investigate the roles of mTORC1 in regulation of the potassium excretion of collecting duct via SGK1 at the molecular, cellular and animal levels and underlying mechanisms. The project will provide new contents for the functions of mTORC1 and mechanisms of potassium excretion and homosis and new targets for prevention and treatment for potassium excretion dysfunction related diseases.