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Bicarbonate and functional CFTR channel are required for proper mucin secretion and link cystic fibrosis with its mucus phenotype.

Journal article
Authors Jenny K Gustafsson
Anna Ermund
Daniel Ambort
Malin E V Johansson
Harriet E Nilsson
Kaisa Thorell
Hans Hebert
Henrik Sjövall
Gunnar C. Hansson
Published in The Journal of experimental medicine
Volume 209
Issue 7
Pages 1263-72
ISSN 1540-9538
Publication year 2012
Published at Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 1263-72
Language en
Keywords Animals, Bicarbonates, pharmacology, Cystic Fibrosis, genetics, metabolism, pathology, Cystic Fibrosis Transmembrane Conductance Regulator, genetics, metabolism, Dose-Response Relationship, Drug, Epithelium, drug effects, metabolism, pathology, Female, Ileum, drug effects, metabolism, ultrastructure, Immunohistochemistry, Intestinal Mucosa, drug effects, metabolism, ultrastructure, Intestine, Small, drug effects, metabolism, pathology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Microscopy, Confocal, Microscopy, Electron, Transmission, Mucins, secretion, Mucus, drug effects, metabolism, Phenotype
Subject categories Basic Medicine, Cell and Molecular Biology


Cystic fibrosis (CF) is caused by a nonfunctional chloride and bicarbonate ion channel (CF transmembrane regulator [CFTR]), but the link to the phenomenon of stagnant mucus is not well understood. Mice lacking functional CFTR (CftrΔ508) have no lung phenotype but show similar ileal problems to humans. We show that the ileal mucosa in CF have a mucus that adhered to the epithelium, was denser, and was less penetrable than that of wild-type mice. The properties of the ileal mucus of CF mice were normalized by secretion into a high concentration sodium bicarbonate buffer (~100 mM). In addition, bicarbonate added to already formed CF mucus almost completely restored the mucus properties. This knowledge may provide novel therapeutic options for CF.

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