Knockout of P2rx7 purinergic receptor attenuates cyst growth in a rat model of ARPKD.

Knockout of P2rx7 purinergic receptor attenuates cyst growth in a rat model of ARPKD. Am J Physiol Renal Physiol. 2019 Oct 21;: Authors: Arkhipov SN, Potter DL, Geurts AM, Pavlov TS Abstract The severity of polycystic kidney diseases depends on the counterbalancing of genetic predisposition and environmental factors exerting permissive or protective influence on cyst development. One poorly characterized phenomenon in the cystic epithelium is abnormal purinergic signaling. Earlier experimental studies revealed high importance of the ionotropic P2X receptors (particularly, P2X7) in the pathophysiology of the cyst wall. To study mechanisms of P2X7 involvement in cyst growth and the aspects of targeting these receptors in PKD treatment we performed a CRISPR/SpCas9-mediated global knockout of the P2rx7 gene in PCK rats, a model of autosomal recessive PKD (ARPKD). A single base insertion in exon 2 of the P2rx7 gene leads to lack of P2X7 protein in the renal tissues of homozygous mutant animals that did not affect their viability or renal excretory function. However, PCK.P2rx7-/- rats demonstrated slower cyst growth (but not formation of new cysts) in comparison to heterozygous and PCK.P2rx7+/+ littermates. P2X7 receptors are known to activate pannexin-1, a plasma channel capable of releasing ATP, and we here found that pannexin-1 expression in cystic epithelium is significantly higher than in non-dilated tubules. P2X7 deficiency reduces r...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research