title: Upregulated expression of ENaC in human CF nasal epithelium.
abstract: Cystic fibrosis (CF) is characterised by the absence of CFTR function resulting in a reduced Cl(-) secretion and an increase in Na+ absorption. This Na+ hyperabsorption is mediated by the human amiloride-sensitive epithelial sodium channel (ENaC), but the underlying mechanisms are still unknown. After demonstrating functional differences of the Na+ absorption in CF and non-CF epithelia in Ussing chamber experiments with human primary cultures, we compared ENaC sequences from CF and non-CF human nasal tissue (hnENaC), investigated the mRNA transcription levels via real-time PCR and studied the protein expression in Western blot analyses. We found no differences in the sequences of CF and non-CF hnENaC, but identified some polymorphisms. The real-time experiments revealed an enhanced mRNA amount of all three hnENaC subunits in CF tissue. By comparing the two groups on the protein level, we observed differences in the abundance of the Na+ channel. While the alpha- and beta-hnENaC protein amount was increased in CF tissue the gamma-hnENaC was decreased. We conclude that the Na+ hyperabsorption in CF is not caused by mutations in hnENaC, but by an increase in the transcription of the hnENaC subunits. This could be induced by a disturbed regulation of the channel in CF.
authors.affiliation: Institute of Animal Physiology, University of Muenster, Hindenburgplatz 55, 48143 Muenster, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Bangel
authors.forename: Christoph
authors.initials: C
authors.lastname: Dahlhoff
authors.forename: Katja
authors.initials: K
authors.lastname: Sobczak
authors.forename: Wolf-Michael
authors.initials: WM
authors.lastname: Weber
authors.forename: Kristina
authors.initials: K
authors.lastname: Kusche-Vihrog
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006801:Humans; D009831:Olfactory Mucosa / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D053503:Epithelial Sodium Channels