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 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 determined that both mTOR kinase inhibitors (TORKs) and sirolimus on decrease PKD and improve kidney function in the Pkd1^RC/RC mouse model. 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
- Dec 01, 2021
- Accession Number
- AD1174936
Entities
People
- Charles L. Edelstein
Organizations
- University of Colorado Health