Bicarbonate and functional CFTR channel are required for proper mucin secretion and link cystic fibrosis with its mucus phenotype.
Journal article, 2012
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.
metabolism
metabolism
Mucus
metabolism
Bicarbonates
Intestinal Mucosa
Mice
Transmission
Drug
Inbred C57BL
Dose-Response Relationship
Intestine
Epithelium
drug effects
metabolism
Mucins
Confocal
Animals
pathology
Mice
drug effects
Female
pathology
Electron
Cystic Fibrosis Transmembrane Conductance Regulator
drug effects
Knockout
Male
ultrastructure
pharmacology
metabolism
pathology
Small
drug effects
drug effects
Phenotype
metabolism
Microscopy
Ileum
Immunohistochemistry
Mice
secretion
ultrastructure
metabolism
genetics
genetics
Microscopy
Cystic Fibrosis
Author
Jenny K Gustafsson
University of Gothenburg
Anna Ermund
University of Gothenburg
Daniel Ambort
University of Gothenburg
Malin E V Johansson
University of Gothenburg
Harriet E Nilsson
Kaisa Thorell
University of Gothenburg
Hans Hebert
Henrik Sjövall
University of Gothenburg
Gunnar C. Hansson
University of Gothenburg
The Journal of experimental medicine
1540-9538 (ISSN)
Vol. 209 7 1263-72Subject Categories
Basic Medicine
Cell and Molecular Biology
DOI
10.1084/jem.20120562
PubMed
22711878