Journal Article

Sodium retention in rats with liver cirrhosis is associated with increased renal abundance of NaCl cotransporter (NCC)

Zhenrong Yu, Andreas Serra, Daniel Sauter, Johannes Loffing, Daniel Ackermann, Felix J. Frey, Brigitte M. Frey and Bruno Vogt

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 20, issue 9, pages 1833-1841
Published in print September 2005 | ISSN: 0931-0509
Published online June 2005 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfh916
Sodium retention in rats with liver cirrhosis is associated with increased renal abundance of NaCl cotransporter (NCC)

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Background. Liver cirrhosis is associated with enhanced renal tubular sodium retention, the mechanism of which is still debated. We hypothesized that liver cirrhosis is associated with increased expression of renal epithelial sodium transporter(s).

Methods. Liver cirrhosis was induced by bile duct ligation (BDL) in rats. Steady state mRNA of ENaC subunits α, β, γ serum and glucocorticoid inducible kinase (Sgk1) were measured by TaqMan PCR in kidney homogenates at week 1, 2, 3 and 4 after BDL. Renal protein content of ENaC subunits, ubiquitin-protein-ligase Nedd4-2 and NaCl cotransporter (NCC) were assessed by western blot. Subcellular localization of ENaC subunits and NCC were analysed by immunohistochemistry.

Results. Steady state mRNA of ENaC α, β and γ were unchanged during the 4 weeks investigated, while ENaC protein decreased most prominently at week 2 (control vs BDL; α, −46%; β, −81%; and γ, −63%; n = 6). Subcellular localization of ENaC subunits was not altered at week 2. Sgk1 mRNA did not change, whereas Nedd4-2 protein was reduced by >50% 2–4 weeks after BDL. NCC protein significantly increased at week 1 (control vs BDL: +66%, n = 6, P<0.05) and decreased at week 3 (control vs BDL: −85%, n = 6, P<0.0005).

Conclusions. Enhanced abundance of NCC was observed in the initial stage after BDL, followed by a marked decrease. ENaC transcription, translation or cell surface abundance was not increased after BDL.

Keywords: epithelial sodium channel (ENaC); bile duct ligation (BDL); liver cirrhosis; Na-Cl cotransporter (NCC); Nedd4-2; serum glucocorticoid inducible kinase 1 (Sgk1)

Journal Article.  4756 words.  Illustrated.

Subjects: Nephrology

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