title: Sodium retention in rats with liver cirrhosis is associated with increased renal abundance of NaCl cotransporter (NCC).
abstract: 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 alpha, beta, gamma 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 alpha, beta and gamma were unchanged during the 4 weeks investigated, while ENaC protein decreased most prominently at week 2 (control vs BDL; alpha, -46%; beta, -81%; and gamma, -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.
authors.affiliation: Division of Nephrology and Hypertension, University Hospital Inselspital, University of Berne, Freiburgstrasse 15, 3010, Berne, Switzerland.
authors.forename: Zhenrong
authors.initials: Z
authors.lastname: Yu
authors.forename: Andreas
authors.initials: A
authors.lastname: Serra
authors.forename: Daniel
authors.initials: D
authors.lastname: Sauter
authors.forename: Johannes
authors.initials: J
authors.lastname: Loffing
authors.forename: Daniel
authors.initials: D
authors.lastname: Ackermann
authors.forename: Felix J
authors.initials: FJ
authors.lastname: Frey
authors.forename: Brigitte M
authors.initials: BM
authors.lastname: Frey
authors.forename: Bruno
authors.initials: B
authors.lastname: Vogt
mesh_terms: D000450:Aldosterone / Q000097:blood; D000818:Animals; D001652:Bile Ducts / Q000502:physiology; D003404:Creatinine / Q000097:blood; D053503:Epithelial Sodium Channels; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008297:Male; D016133:Polymerase Chain Reaction; D011188:Potassium / Q000652:urine; D021122:Protein Subunits / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000378:metabolism* / Q000652:urine; D015222:Sodium Channels / Q000235:genetics*; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics* / Q000378:metabolism*
chemical_list: D053503:Epithelial Sodium Channels; D021122:Protein Subunits; D012333:RNA, Messenger; D015222:Sodium Channels; D028021:Sodium-Potassium-Chloride Symporters; D000450:Aldosterone; D012964:Sodium; D003404:Creatinine; D011188:Potassium