Could a defective epithelial sodium channel lead to bronchiectasis
Isabelle Fajac1, Marion Viel, Sébastien Sublemontier
1Service d'Explorations Fonctionnelles, AP-HP, Hôpital Cochin, Paris, France. ifajac@cochin.univ-paris5.fr
Respiratory Research
|May 30, 2008
Summary
Defective epithelial sodium channel (ENaC) variants may contribute to bronchiectasis development, particularly in individuals with co-occurring CFTR gene mutations. This research explores ENaC
Area of Science:
- Pulmonary Medicine
- Genetics
- Molecular Biology
Background:
- Bronchiectasis is airway dilation from chronic inflammation, often with unknown causes.
- Cystic fibrosis, linked to CFTR gene mutations, causes bronchiectasis and involves the epithelial sodium channel (ENaC).
- Transgenic mice overexpressing ENaCbeta exhibit cystic fibrosis-like lung disease, suggesting ENaC's role.
Purpose of the Study:
- To investigate the potential involvement of defective ENaC protein in the development of bronchiectasis.
- To analyze ENaCbeta and gamma genes in patients with idiopathic bronchiectasis.
Main Methods:
- Sequencing of ENaCbeta and gamma genes in 55 patients with idiopathic bronchiectasis and no CFTR mutations.
- Analysis of patients with and without functional abnormalities indicating impaired sodium transport.
Main Results:
- Five distinct amino-acid changes in ENaCbeta and ENaCgamma were identified in 8 patients.
- One variant (p.Ser82Cys) was found in three unrelated patients who also carried CFTR mutations/variants.
- Other variants were found in patients without CFTR mutations; five of the eight patients showed impaired sodium transport.
Conclusions:
- ENaCbeta and ENaCgamma gene variants may impair ENaC function, potentially leading to bronchiectasis.
- This risk is heightened in patients with trans-heterozygous ENaCbeta/CFTR mutations or variants.
- Further research is warranted to elucidate the precise mechanisms linking ENaC dysfunction to bronchiectasis.
Related Concept Videos
01:23Cystic Fibrosis: Pathogenesis
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
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...
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...
01:24Chronic Obstructive Pulmonary Disease III: Chronic Bronchitis Features
Chronic bronchitis is a key phenotype of chronic obstructive pulmonary disease (COPD), characterized by airway-centered inflammation and mucus overproduction. It develops from long-term exposure to harmful particles or gases, most commonly cigarette smoke, which triggers a persistent inflammatory response.Cellular and Structural ChangesInflammation initially affects the large bronchi and later the smaller airways, with infiltration by immune cells, including neutrophils, macrophages, and...
01:23Chronic Obstructive Pulmonary Disease II: Emphysema
Emphysema, a major phenotype of chronic obstructive pulmonary disease (COPD), is characterized by irreversible destruction of alveolar walls and permanent enlargement of distal airspaces. Unlike chronic bronchitis, which primarily affects the airways, emphysema predominantly involves the lung parenchyma, where structural damage leads to airflow limitation.PathophysiologyIt most commonly results from prolonged exposure to cigarette smoke and other toxic gases, particularly cigarette smoke.
01:23The Bronchial Tree
The human bronchi and bronchial tree play a crucial role in the respiratory system, facilitating the exchange of oxygen and carbon dioxide. Let's delve into the intricate structure and functions of these respiratory components.
The trachea, commonly known as the windpipe, is a tube that connects the larynx (voice box) to the bronchi. At a point called the carina, it bifurcates into two primary bronchi. The right primary bronchus is wider, shorter, and more vertical than the left primary...
The trachea, commonly known as the windpipe, is a tube that connects the larynx (voice box) to the bronchi. At a point called the carina, it bifurcates into two primary bronchi. The right primary bronchus is wider, shorter, and more vertical than the left primary...
01:28Asthma I: Introduction
Asthma is a chronic inflammatory disorder of the airways characterized by variable airflow obstruction and heightened bronchial responsiveness to a wide range of triggers. The underlying inflammation leads to airway swelling, mucus hypersecretion, and smooth muscle constriction, all of which narrow the airway lumen and impede airflow. Clinically, asthma presents with recurrent episodes of wheezing, shortness of breath, chest tightness, and coughing, symptoms that typically vary in intensity and...
01:20Asthma: Pathogenesis and Management
Asthma is a chronic pulmonary condition involving inflammation of the airways, hyper-reactivity, and reversible obstruction of the airways. This condition can significantly impact a person's quality of life, making breathing difficult and leading to distressing symptoms.
Asthma is classified as allergic and non-allergic. Allergens such as dust mites, pollen, and pet dander trigger allergic asthma, while factors like cold air, intense emotions, or exercise can induce non-allergic asthma.
Asthma is classified as allergic and non-allergic. Allergens such as dust mites, pollen, and pet dander trigger allergic asthma, while factors like cold air, intense emotions, or exercise can induce non-allergic asthma.