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Aryl hydrocarbon receptor deficiency causes the development of chronic obstructive pulmonary disease through the integration of multiple pathogenic mechanisms
- Source :
- FASEB J, FASEB Journal, 35(3):21376. FEDERATION AMER SOC EXP BIOL
- Publication Year :
- 2021
-
Abstract
- Emphysema, a component of chronic obstructive pulmonary disease (COPD), is characterized by irreversible alveolar destruction that results in a progressive decline in lung function. This alveolar destruction is caused by cigarette smoke, the most important risk factor for COPD. Only 15%-20% of smokers develop COPD, suggesting that unknown factors contribute to disease pathogenesis. We postulate that the aryl hydrocarbon receptor (AHR), a receptor/transcription factor highly expressed in the lungs, may be a new susceptibility factor whose expression protects against COPD. Here, we report that Ahr-deficient mice chronically exposed to cigarette smoke develop airspace enlargement concomitant with a decline in lung function. Chronic cigarette smoke exposure also increased cleaved caspase-3, lowered SOD2 expression, and altered MMP9 and TIMP-1 levels in Ahr-deficient mice. We also show that people with COPD have reduced expression of pulmonary and systemic AHR, with systemic AHR mRNA levels positively correlating with lung function. Systemic AHR was also lower in never-smokers with COPD. Thus, AHR expression protects against the development of COPD by controlling interrelated mechanisms involved in the pathogenesis of this disease. This study identifies the AHR as a new, central player in the homeostatic maintenance of lung health, providing a foundation for the AHR as a novel therapeutic target and/or predictive biomarker in chronic lung disease.
- Subjects :
- 0301 basic medicine
Male
SOD2
Disease
MMP9
Biochemistry
Article
Pathogenesis
03 medical and health sciences
Mice
Pulmonary Disease, Chronic Obstructive
0302 clinical medicine
Forced Expiratory Volume
Genetics
Medicine
Animals
Humans
Receptor
Molecular Biology
Lung
Aged
Aged, 80 and over
Emphysema
COPD
biology
business.industry
Aryl Hydrocarbon Receptor Nuclear Translocator
Smoking
Middle Aged
respiratory system
medicine.disease
Aryl hydrocarbon receptor
3. Good health
respiratory tract diseases
030104 developmental biology
Receptors, Aryl Hydrocarbon
Immunology
biology.protein
business
030217 neurology & neurosurgery
Homeostasis
Biotechnology
Subjects
Details
- Language :
- English
- ISSN :
- 08926638
- Volume :
- 35
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- FASEB Journal
- Accession number :
- edsair.doi.dedup.....04f41cd7b9a4e41e4b10bdfe53e22f72