A study of sirolimus and mTOR kinase inhibitor in a hypomorphic Pkdl mouse model of autosomal dominant polycystic kidney disease

摘要

Autosomal dominant polycystic kidney disease (PKD) is characterized by cyst formation and growth, which are partially driven by abnormal proliferation of tubular cells. Proproliferative mechanistic target of rapamycin (mTOR) complexes 1 and 2 (mTORCl and mTORC2) are activated in the kidneys of mice with PKD. Sirolimus indirectly inhibits mTORCl. Novel mTOR kinase inhibitors directly inhibit mTOR kinase, resulting in the inhibition of mTORCl and mTORC2.