Novel mTORC1 and 2 Signaling Pathways in Polycystic Kidney Disease (PKD)
Abstract
This proposal will study novel mTORC1 and 2 signaling pathways that mediate ADPKD and investigate the effects of mTORC1 (Raptor) knockout, mTORC2 (Rictor) knockout or combined mTORC1 and 2 knockout on cyst growth and kidney function. The overall hypothesis is that there is increased mTORC1 (4E-BP1) and mTORC2 (AktSer473, PKCalpha and SGK1) signaling in PKD kidneys and that combined mTORC1 (Raptor) knockout and mTORC2 (Rictor) knockout in Pkd1 -/- mice will slow cyst growth and improve kidney function more than mTORC1 (Raptor) knockout or mTORC2 (Rictor) knockout alone. We have made significant progress in the fourth year: We have published the role 4E-BP1 signaling pathways in PKD kidneys and cells. We have preliminary data in Pkd1, Rictor double knockout mice. We have published: 1) The effect of trehalose on mTOR signaling and autophagy in PKD kidneys, 2) mTOR signaling and autophagy in the heart and kidney in PKD. We have continued to use FISP-MRI scanning to obtain precise measurements of kidney and cyst volume and the number of cysts in live PKD mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2020
- Accession Number
- AD1111962
Entities
People
- Charles L. Edelstein
Organizations
- University of Colorado Denver