Abstract | BACKGROUND: OBJECTIVE: Because cigarette smoke is the major risk factor for COPD, we aimed to investigate the role of ORMDL3 in cigarette smoke-induced human airway smooth muscle cell (HASMC) injury. METHODS: The mRNA and protein expression of ORMDL3 was examined in HASMCs from nonsmokers and smokers without or with COPD. Knockdown of ORMDL3 in primary healthy HASMCs was performed using small interfering RNA before exposure to cigarette smoke medium (CSM) for 24 hours. Inflammatory, proliferative/apoptotic, ER stress, and mitochondrial markers were evaluated. RESULTS: Elevation of ORMDL3 mRNA and protein expression was observed in HASMCs of smokers without or with COPD. CSM caused significant upregulation of ORMDL3 expression in healthy nonsmokers. ORMDL3 knockdown regulated CSM-induced inflammation, cell proliferation, and apoptosis. Silencing ORMDL3 led to reduction of CSM-induced ER stress via inhibition of unfolded protein response pathways such as activating transcription factor 6 and protein kinase RNA-like ER kinase. ORMDL3 was also involved in CSM-induced mitochondrial dysfunction via the mitochondrial fission process. CONCLUSIONS: We report the induction of ORMDL3 in HASMCs after cigarette smoke exposure. ORMDL3 may mediate cigarette smoke-induced activation of unfolded protein response pathways during airway smooth muscle cell injury.
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Authors | Rui Chen, Charalambos Michaeloudes, Yingmin Liang, Pankaj K Bhavsar, Kian Fan Chung, Mary S M Ip, Judith C W Mak |
Journal | The Journal of allergy and clinical immunology
(J Allergy Clin Immunol)
Vol. 149
Issue 4
Pg. 1445-1457.e5
(04 2022)
ISSN: 1097-6825 [Electronic] United States |
PMID | 34624393
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Membrane Proteins
- ORMDL3 protein, human
- RNA, Messenger
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Topics |
- Asthma
(metabolism)
- Child
- Cigarette Smoking
(adverse effects)
- Endoplasmic Reticulum Stress
- Humans
- Membrane Proteins
(genetics, metabolism)
- Myocytes, Smooth Muscle
(metabolism)
- Pulmonary Disease, Chronic Obstructive
(genetics)
- RNA, Messenger
(metabolism)
- Nicotiana
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