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Role of the epithelial Na + channels (ENaC) in development of ARPKD
Author(s) -
Pavlov Tengis S,
Levchenko Vladislav,
Ilatovskaya Daria V,
Palygin Oleg,
Staruschenko Alexander
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1148.1
Subject(s) - epithelial sodium channel , reabsorption , autosomal recessive polycystic kidney disease , endocrinology , medicine , nephron , amiloride , epidermal growth factor , kidney , cyst , polycystic kidney disease , pendrin , apical membrane , biology , epithelium , pathology , chemistry , receptor , sodium , biochemistry , gene , organic chemistry , transporter
Autosomal recessive polycystic kidney disease (ARPKD) is characterized by the development of renal cysts of tubular epithelial cell origin. Dysfunction and aberrant regulation of the epithelial Na + channel (ENaC) lead to a spectrum of diseases ranging from hyper‐and hypotension associated with improper renal Na + conservation and wasting, respectively, to cystic fibrosis. Members of the epidermal growth factor (EGF) family have direct actions on Na + reabsorption in the distal nephron. It has also been reported that EGF receptor (EGFR) is overexpressed and mislocalized to the apical membranes in the cystic epithelia. Here we tested whether ENaC plays a role in the cyst development in PCK rats, model of ARPKD. 4 and 12 weeks treatment with ENaC inhibitor benzamil caused more severe cyst formation in PCK rats. Patch clamp studies of ENaC in freshly isolated cysts and immunohistochemical analysis confirm that ENaC expression and activity are modulated in the freshly isolated cysts of PCK compared to benzamil‐treated and noncystic collecting duct. We conclude that abnormal EGF signaling leads to inappropriately low ENaC activity which contributes to cyst formation in PCK rats. Thus, the disruption of the EGF‐EGFR axis reported in PKD is linked to suppression of normal Na + reabsorption and further progress of this kidney disease. Supported by the AHA 10POST4140109; ADA 1–10‐BS‐168; NIH HL108880.