Faculty Collaboration Database

Impaired epithelial Na+ channel activity contributes to cystogenesis and development of autosomal recessive polycystic kidney disease in PCK rats. Pediatr Res 2015 Jan;77(1-1):64-9

Date

10/04/2014

Pubmed ID

25279988

Pubmed Central ID

PMC4268054

DOI

10.1038/pr.2014.145

Scopus ID

2-s2.0-84927926394 (requires institutional sign-in at Scopus site)   22 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.

Author List

Pavlov TS, Levchenko V, Ilatovskaya DV, Palygin O, Staruschenko A

MESH terms used to index this publication - Major topics in bold

Aldosterone
Amiloride
Animals
Aquaporin 2
Disease Models, Animal
Disease Progression
Epithelial Sodium Channels
Immunohistochemistry
Kidney
Patch-Clamp Techniques
Polycystic Kidney, Autosomal Recessive
Rats
Rats, Sprague-Dawley
Sodium