Decreased β₁ Na⁺ - K⁺ ATPase subunit expression and defective focal adhesion kinase activation mediate disturbed cell polarity in autosomal recessive polycystic kidney disease

Mohamed S. A. Mohamed

Department of Pediatrics Nephrology, MHH, Carl-Neuberg-Strae 1, D-30625 Hannover, Germany.

E-mail: Mohamed.Shehata@uk-essen.de, mohammed.shehatta1@gmail.com

Accepted 01 October, 2014

Abstract

ARPKD is a developmental disease that results from fibrocystin loss of function mutation. It affects mainly renal collecting ducts and biliary system. The exact mechanism of how fibrocystin mutation results in the disease manifestations is not known as the exact functions of fibrocystin are also not known. However, this hypothesis explains one of the major mechanisms that may be involved in ARPKD development based on a group of proved observations in previous publications. The impaired epithelial cellular polarity seen in ARPKD might result from impaired β₁ / β₂ Na⁺- K⁺ ATPase expression together with impaired FAK activation and functions, with possible involvement of adhesion signaling in development of those interactions. Expression of β₁ Na⁺- K⁺ ATPase subunit is necessary for E- cadherin mediated establishment of epithelial cell polarity. Focal adhesion kinase interacts with adhesion proteins and is essential for establishment of polarized cell migration. Both together may explain how fibrocystin loss of function mutation can result in reversed epithelial cell polarity which proceeds to intracystic secretion in ARPKD.

Keywords: ARPKD, Fibrocystin, FAK, Na⁺ - K⁺ ATPase, and epithelial cell polarity.