Lipid Peroxidation Drives Renal Cyst Growth In Vitro through Activation of TMEM16A.

ABSTRACT:

Background

Transepithelial chloride^- secretion, through the chloride channels cystic fibrosis transmembrane conductance regulator (CFTR) and TMEM16A (anoctamin 1), drives cyst enlargement in polycystic kidney disease (PKD). Polycystic kidneys are hypoxic, and oxidative stress activates TMEM16A. However, mechanisms for channel activation in PKD remain obscure.

Methods

Using tissue samples from patients with autosomal dominant PKD, embryonic kidney cultures, and an MDCK in vitro cyst model, we assessed peroxidation of plasma membrane phospholipids in human and mouse polycystic kidneys. We also used electrophysiologic Ussing chamber and patch clamp experiments to analyze activation of TMEM16A and growth of renal cysts.

Results

Peroxidation of phospholip

SUBMITTER: Schreiber R 

PROVIDER: S-EPMC6362630 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature