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.
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: David Mordasini; Dominique Loffing-Cueni; Johannes Loffing; Rohrbach Beatrice; Marc P Maillard; Edith Hummler; Michel Burnier; Geneviève Escher; Bruno Vogt Journal: Pflugers Arch Date: 2015-06-10 Impact factor: 3.657
Authors: Nicolas Picard; Katja Trompf; Chao-Ling Yang; R Lance Miller; Monique Carrel; Dominique Loffing-Cueni; Robert A Fenton; David H Ellison; Johannes Loffing Journal: J Am Soc Nephrol Date: 2013-11-14 Impact factor: 10.121