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• W2932296166 abstract "Genetic predisposition is necessary for polycystic kidney disease (PKD) initiation, although there are other, incompletely identified downstream processes that are required for cyst growth. Their characterization may provide a unique opportunity for clinical interventions. One of the poorly studied phenomena in PKD is high ATP content in cysts. Unfortunately, neither origins of uncontrolled ATP release, nor consequences of abnormal purinergic signaling in relation to epithelial transport are well explored in the polycystic kidney. We tested the distribution of pannexin-1 (Panx1) and P2X7, two proteins potentially involved in ATP release, in the kidneys of the Pkd1RC/RC mice, a model of autosomal dominant PKD (ADPKD). Abundances of both proteins were abnormally increased in the cyst lining cells compared to non-dilated collecting ducts. To establish if pannexin-1 contributes to ATP release in the collecting ducts (CD), we measured luminal accumulation of ATP in M1 cell renal CD monolayers, and found that treatment with probenecid, a Panx1 blocker, prevents ATP release. Single channel patch clamp analysis of polarized M1 cells revealed that apical stimulation of P2X receptors with αβ-MeATP acutely reduces ENaC activity. We conclude that in ADPKD progression, an abnormal hyperexpression of both PANX1 and P2RX7 occurs in the cyst lining epithelial cells. High abundance of both proteins is not typical for non-dilated CDs but, when it happens in cysts, pannexin1/P2X7 cooperation elevates ATP release into the luminal space. High ATP level is a pathogenic factor facilitating cystogenesis by reducing ENaC-mediated reabsorption from the lumen." @default.
• W2932296166 created "2019-04-11" @default.
• W2932296166 creator A5033227240 @default.
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• W2932296166 date "2019-05-01" @default.
• W2932296166 modified "2023-10-17" @default.
• W2932296166 title "ATP release into ADPKD cysts via pannexin-1/P2X7 channels decreases ENaC activity" @default.
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• W2932296166 doi "https://doi.org/10.1016/j.bbrc.2019.03.177" @default.
• W2932296166 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6475605" @default.
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