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Updated: Jun 28, 2026
07:13
Phenotyping Mouse Pulmonary Function In Vivo with the Lung Diffusing Capacity
Published on: January 6, 2015
Impact of ΔF508 CFTR mutation on diaphragm function during acute inflammation
Fatemeh Ostadan1, Ekaterina Gusev1, Feng Liang1
1Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, Canada.
American Journal of Physiology. Cell Physiology
|June 26, 2026
Summary
Mice with the cystic fibrosis (CF) ΔF508 mutation show increased diaphragm oxidative stress and proteolysis during inflammation, leading to greater force loss. This suggests higher vulnerability to diaphragm dysfunction in CF patients.
Area of Science:
- Physiology
- Molecular Biology
- Pathology
Background:
- Cystic fibrosis (CF) results from CFTR mutations, leading to skeletal muscle dysfunction.
- Previous studies indicated heightened inflammatory proteolysis in CFTR-null mouse diaphragms.
- The impact of the common ΔF508 (DF-CFTR) mutation on diaphragm function remains unclear.
Purpose of the Study:
- To investigate the effects of the DF-CFTR mutation on diaphragm function and molecular responses to inflammation.
- To compare diaphragm responses between homozygous DF-CFTR mice and wild-type littermates under baseline and lipopolysaccharide (LPS)-induced inflammatory conditions.
Main Methods:
- Utilized homozygous DF-CFTR and wild-type mice, administering PBS or LPS.
- Assessed diaphragm mass, fiber types, gene expression (cytokines, UPR, proteolysis pathways), calpain activity, oxidative stress markers, and ex vivo contractility.
- Analyzed ubiquitin-proteasome and autophagy-lysosome pathways, including Atrogin1 and LC3B.
Main Results:
- DF-CFTR diaphragms exhibited elevated oxidative stress at baseline and post-LPS.
- LPS induced stronger Atrogin1 and autophagy marker expression in DF-CFTR diaphragms.
- Only DF-CFTR diaphragms showed reduced force production after LPS challenge, despite no differences in mass or fiber type.
Conclusions:
- DF-CFTR diaphragms display exaggerated oxidative stress and proteolysis signaling during acute inflammation.
- These molecular changes correlate with increased diaphragm force loss in response to inflammatory stimuli.
- Findings suggest an enhanced susceptibility to diaphragm dysfunction associated with the DF-CFTR mutation in cystic fibrosis.
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