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, PKC 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 second year: We have further characterized 4E-BP1 signaling pathways in PKD kidneys and cells. We have continued to breed Pkd1-/-, mTORC2 (Rictor) -/- double knockout mice but have changed our breeding system. We have performed a head to head study to compare the therapeutic effect of the mTOR kinase inhibitor Torin-2 (that inhibits both mTORC1 and mTORC2) with sirolimus (that inhibits mTORC1) on cyst growth and kidney function.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2018
Accession Number
AD1061766

Entities

People

  • Charles L. Edelstein

Organizations

  • University of Colorado Denver

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Biomedical Research
  • Cells
  • Department Of Defense
  • Diseases And Disorders
  • Epithelial Cells
  • Gene Therapy
  • Inhibition
  • Inhibitors
  • Kidney Diseases
  • Medical Personnel
  • Professional Development
  • Proteins
  • Side Effects
  • Students
  • Therapy
  • Virotherapy

Readers

  • Aquatic Ecology
  • Molecular and Cellular Biology