Impaired epithelial Na + channel activity contributes to cystogenesis and development of autosomal recessive polycystic kidney disease in PCK rats

Tengis S. Pavlov, Vladislav Levchenko, Daria V. Ilatovskaya, Oleg Palygin, Alexander Staruschenko

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Background:Autosomal recessive polycystic kidney disease is a genetic disorder characterized by the development of renal cysts of tubular epithelial cell origin. Epithelial Na + channel (ENaC) is responsible for sodium reabsorption in the aldosterone-sensitive distal nephron. Here, we investigated the ENaC expression and activity in cystic tissue taken from rats with autosomal recessive polycystic kidney disease.Methods:Polycystic kidney (PCK) rats were treated with the selective ENaC inhibitor benzamil given in the drinking water, and after 4 or 12 wk, the severity of morphological malformations in the kidneys was assessed. ENaC and aquaporin-2 expression and ENaC activity were tested with immunohistochemistry and patch-clamp electrophysiology, respectively.Results:Treatment with benzamil exacerbated development of cysts compared with the vehicle-treated animals. In contrast, the 12 wk of treatment with the loop diuretic furosemide had no effect on cystogenesis. Single-channel patch-clamp analysis revealed that ENaC activity in the freshly isolated cystic epithelium was significantly lower than that in the noncystic collecting ducts isolated from PCK or normal Sprague-Dawley rats. Immunohistochemical analysis confirmed that β-ENaC and aquaporin-2 expressions in cysts are decreased compared with nondilated tubules from PCK rat kidneys.Conclusion:We demonstrated that cystic epithelium exhibits low ENaC activity and this phenomenon can contribute to cyst progression.

Original languageEnglish (US)
Pages (from-to)64-69
Number of pages6
JournalPediatric research
Volume77
Issue number1
DOIs
StatePublished - 2015
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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