Protein Kinase A Downregulation Delays the Development and Progression of Polycystic Kidney Disease.

ABSTRACT:

Background

Upregulation of cAMP-dependent and cAMP-independent PKA signaling is thought to promote cystogenesis in polycystic kidney disease (PKD). PKA-I regulatory subunit RIα is increased in kidneys of orthologous mouse models. Kidney-specific knockout of RIα upregulates PKA activity, induces cystic disease in wild-type mice, and aggravates it in Pkd1^RC/RC mice.

Methods

PKA-I activation or inhibition was compared with EPAC activation or PKA-II inhibition using Pkd1^RC/RC metanephric organ cultures. The effect of constitutive PKA (preferentially PKA-I) downregulation in vivo was ascertained by kidney-specific expression of a dominant negative RIαB allele in Pkd1^RC/RC mice obtained by crossing <

SUBMITTER: Wang X 

PROVIDER: S-EPMC9161799 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature