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Defining an olfactory receptor function in airway smooth muscle cells
William H Aisenberg1, Jessie Huang2, Wanqu Zhu2
1Department of Physiology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Scientific Reports
|December 2, 2016
Summary
Researchers discovered a novel gut-lung signaling pathway in airway smooth muscle (ASM). Targeting the odorant receptor OR51E2 with short-chain fatty acids may treat asthma by reducing ASM remodeling and proliferation.
Area of Science:
- Pulmonary Medicine
- Cellular Biology
- Gastroenterology
Background:
- Asthma pathogenesis involves airway smooth muscle (ASM) mass increase and remodeling.
- Pathways regulating ASM remodeling are not fully understood.
- Odorant receptors (ORs) are G-protein coupled receptors (GPCRs) primarily known for olfaction.
Purpose of the Study:
- To investigate the presence and function of ORs in human ASM.
- To explore the role of OR51E2 and its ligands in regulating ASM cellular processes.
- To identify novel therapeutic targets for asthma.
Main Methods:
- Analysis of mRNA expression of ORs and olfactory machinery (Golf, AC3) in human bronchial ASM.
- Primary culture of human ASM cells for functional studies.
- Heterologous expression system to characterize OR51E2.
- Assays to measure cytoskeletal remodeling and proliferation of ASM cells upon stimulation with short-chain fatty acids (SCFAs).
Main Results:
- Multiple ORs, including highly enriched OR51E2, were detected in human ASM.
- OR51E2 responded to SCFAs (acetate, propionate), which are gut microbiota metabolites.
- SCFAs inhibited cytoskeletal remodeling and proliferation in human ASM cells.
- These effects were dependent on OR51E2 expression.
Conclusions:
- A novel chemo-mechanical signaling network exists in ASM involving ORs and gut-derived metabolites.
- OR51E2 acts as a sensor for SCFAs in ASM.
- Targeting the OR51E2-SCFA axis presents a potential therapeutic strategy for asthma by modulating ASM remodeling and airflow obstruction.
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