Related Experiment Video
Updated: Jul 3, 2026

Standardized Measurement of Nasal Membrane Transepithelial Potential Difference (NPD)
Published on: September 13, 2018
Deficiency of Mitochondrial Fatty Acid Enzyme, CPT1A, Underlies Airway Epithelial Barrier Dysfunction in Severe
Muyun Wang1, Haiyang Hu2, Kun Wang1
1Department of Respiratory and Critical Care Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Background:
Mitochondrial fatty acid oxidation through carnitine palmitoyltransferase-1A (CPT1A) leads to ATP generation. We examined its role in regulating permeability and mitochondrial metabolic homeostasis of airway epithelial cells in asthma.
Methods:
Primary nasal epithelial cells (NECs) from healthy controls and severe asthma (SA) patients in air-liquid interface (ALI) were exposed to CPT1A siRNA/CPT1A overexpression lentiviral/L-carnitine (LCA). Epithelial TEER and FITC-dextran transport were measured. Bronchial biopsies from healthy and SA subjects and house dust mite (HDM) asthma mouse model were also studied.
Results:
In NECs-ALI and in bronchial epithelial cells (BECs) from bronchial biopsies of SA, CPT1A expression was reduced compared to healthy controls. Knock-down of CPT1A in healthy NECs reduced expression of Occludin and E-cadherin and impaired epithelial barrier integrity (EBI), while upregulation of CPT1A with CPT1A overexpression lentiviral/LCA in SA-NECs increased the barrier proteins with improved EBI. CPT1A knockdown in healthy BECs increased release of mtROS, with mitochondrial disruption and activation of ERK1/2-NF-κB signaling pathway. These were aggravated with HDM exposure but N-acetyl-cysteine and MitoTempo reduced p-ERK1/2 and p-P65 activation, as well as EBI with CPT1A knockdown and HDM. In the mouse model, there was decreased airway epithelial CPT1A protein expression, associated with reduced airway hyperreactivity and inflammation, and in Occludin and ZO-1 expression, effects partly reversed by LCA, with restoration of mitochondrial integrity and EBI.
Conclusion:
CPT1A maintains epithelial barrier function through restoration of mitochondrial function in asthmatic airway epithelial cells. Restoration of deficient epithelial CPT1A of SA may represent a new treatment approach.
Related Concept Videos
Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...
Chronic Obstructive Pulmonary Disease-II: Pathophysiology
Chronic Inflammation
Chronic Obstructive Pulmonary Disease III: Chronic Bronchitis Features
Chronic Obstructive Pulmonary Disease II: Emphysema
Cystic Fibrosis: Management
Sinus disease and chronic sinusitis...
Chronic Obstructive Pulmonary Disease I: Introduction
