Abnormal purinergic signaling contributes to development of renal cysts in autosomal dominant polycystic kidney disease.

ABSTRACT: Polycystic kidney diseases (PKD) are a group of inherited nephropathies marked by the formation of fluid-filled cysts along the nephron, which cause renal failure. Bulk RNA sequencing of microdissected renal cysts from Pkd1^RC/RC mice identifies 4,970 differentially expressed genes in comparison to intact collecting ducts. A poorly understood factor of cyst growth is the high ATP level in the cyst fluid, probably released by pannexin-1 hemichannels. Here, we evaluate a novel pannexin-1 inhibitor SIL14 as a potential therapeutic agent for cyst reduction and investigate proteins involved in cystogenesis, with a focus on purinergic signaling. In patch-clamp experiments, acute SIL14 application demonstrated strong, dose-dependent inhibition of Pannexin-1-dependent currents (IC₅₀

SUBMITTER: Ivanov V 

PROVIDER: S-EPMC12819920 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature