Probenecid slows disease progression in a murine model of autosomal dominant polycystic kidney disease.

ABSTRACT: Development of autosomal dominant polycystic kidney disease (ADPKD) involves renal epithelial cell abnormalities. Cystic fluid contains a high level of ATP that, among other effects, leads to a reduced reabsorption of electrolytes in cyst-lining cells, and thus results in cystic fluid accumulation. Earlier, we demonstrated that Pkd1^RC/RC mice, a hypomorphic model of ADPKD, exhibit increased expression of pannexin-1, a membrane channel capable of ATP release. In the current study, we found that human ADPKD cystic epithelia have higher pannexin-1 abundance than normal collecting ducts. We hypothesized that inhibition of pannexin-1 function with probenecid can be used to attenuate ADPKD development. Renal function in male and female Pkd1^RC/RC and control mice was monitor

SUBMITTER: Arkhipov SN 

PROVIDER: S-EPMC10079433 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature