Age-Dependent Progression in Lung Pathophysiology can be Prevented by Restoring Fatty Acid and Ceramide Imbalance in Cystic Fibrosis.
Lung
; 198(3): 459-469, 2020 06.
Article
in En
| MEDLINE
| ID: mdl-32306138
ABSTRACT
PURPOSE:
Cystic fibrosis (CF) is a progressive disease which causes a continuous decline in lung capacity with age. Our study aimed to investigate the age-dependent deterioration in lung function and the effects of treatment with Fenretinide formulation (LAU-7b) in Cftr knockout (KO) mice.METHODS:
Non-invasive whole-body plethysmography (WBP) was done to measure the baseline lung functions of KO and wild-type (WT) mice at the ages of 2 and 4 months. Mice were then treated for 21 days with PBS or 10 mg/kg/day LAU-7b initiated at 4 and 7 months. Standard airway resistance measurements, haematoxylin and eosin staining, and analysis of lipids, and markers of oxidation were performed.RESULTS:
The 4- and 7-month-old KO mice had significantly higher lung enhanced pause (Penh) and resistance values than age-matched WT mice and 2-month-old KO mice. Likewise, analysis of ceramides showed that PBS-treated mice had higher levels of long-chain ceramides (LCCs; C14-C18) and lower levels of very-long-chain ceramides (VLCCs; C24-C26) compared to LAU-7b-treated mice. Cftr KO mice displayed markedly greater inflammatory cell infiltration and epithelial hyperplasia at the ages of 2, 4, and 7 months compared to WT. LAU-7b treatment significantly diminished this cellular infiltration and epithelial hyperplasia compared to PBS-treated mice.CONCLUSION:
Our results demonstrate a progressive age-dependent decline in lung function in Cftr KO mice. Treatment with LAU-7b corrects the lipid imbalance observed in the aging KO and WT mice and, more importantly, inhibits the age-dependent deterioration in lung physiology and histopathology.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aging
/
Ceramides
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Airway Resistance
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Cystic Fibrosis
/
Fatty Acids
/
Lung
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Lung
Year:
2020
Document type:
Article
Affiliation country: