Mordasini, David; Loffing-Cueni, Dominique; Loffing, Johannes; Rohrbach, Beatrice; Maillard, Marc; Hummler, Edith; Burnier, Michel; Escher, Geneviève; Vogt, Bruno (2015). ENaC activity in collecting ducts modulates NCC in cirrhotic mice. Pflügers Archiv : European journal of physiology, 467(12), pp. 2529-2539. Springer 10.1007/s00424-015-1711-7
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Cirrhosis is a frequent and severe disease, complicated by renal sodium retention leading to ascites and oedema. A better understanding of the complex mechanisms responsible for renal sodium handling could improve clinical management of sodium retention. Our aim was to determine the importance of the amiloride-sensitive epithelial sodium channel (ENaC) in collecting ducts in compensate and decompensate cirrhosis. Bile duct ligation was performed in control mice (CTL) and collecting duct-specific αENaC knockout (KO) mice, and ascites development, aldosterone plasma concentration, urinary sodium/potassium ratio and sodium transporter expression were compared. Disruption of ENaC in collecting ducts (CDs) did not alter ascites development, urinary sodium/potassium ratio, plasma aldosterone concentrations or Na,K-ATPase abundance in CCDs. Total αENaC abundance in whole kidney increased in cirrhotic mice of both genotypes and cleaved forms of α and γ ENaC increased only in ascitic mice of both genotypes. The sodium chloride cotransporter (NCC) abundance was lower in non-ascitic KO, compared to non-ascitic CTL, and increased when ascites appeared. In ascitic mice, the lack of αENaC in CDs induced an upregulation of total ENaC and NCC and correlated with the cleavage of ENaC subunits. This revealed compensatory mechanisms which could also take place when treating the patients with diuretics. These compensatory mechanisms should be considered for future development of therapeutic strategies.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Nephrologie / Hypertonie 04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension |
UniBE Contributor: |
Mordasini, David, Rohrbach, Beatrice, Escher, Geneviève, Vogt, Bruno |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1432-2013 |
Publisher: |
Springer |
Funders: |
[4] Swiss National Science Foundation |
Language: |
English |
Submitter: |
Geneviève Escher |
Date Deposited: |
07 Apr 2016 14:47 |
Last Modified: |
05 Dec 2022 14:54 |
Publisher DOI: |
10.1007/s00424-015-1711-7 |
PubMed ID: |
26055235 |
Uncontrolled Keywords: |
Ascites; Aldosterone; Cirrhosis; Cortical collecting ducts; ENaC; NCC |
BORIS DOI: |
10.7892/boris.79738 |
URI: |
https://boris.unibe.ch/id/eprint/79738 |
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