Defining an olfactory receptor function in airway smooth muscle cells
| Autor: | Reynold A. Panettieri, A-Rum Yoon, Cruz R, Steven S. An, Wanqu Zhu, De Santiago B, Oliver Homann, William H. Aisenberg, Hwan Mee Yong, Stephen B. Liggett, Jennifer L. Pluznick, Rajkumar P, Lakshmi Santhanam, Oh Jj, Sullivan Jk, Niranjana Natarajan, Jessie Huang |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Myocytes Smooth Muscle Cell Bronchi Receptors Odorant Mechanotransduction Cellular Article 03 medical and health sciences medicine Humans Myocyte Mechanotransduction Cytoskeleton Receptor G protein-coupled receptor Multidisciplinary Olfactory receptor Chemistry respiratory system Asthma Neoplasm Proteins respiratory tract diseases 3. Good health Cell biology 030104 developmental biology medicine.anatomical_structure Heterologous expression |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep38231 |
| Popis: | Pathways that control, or can be exploited to alter, the increase in airway smooth muscle (ASM) mass and cellular remodeling that occur in asthma are not well defined. Here we report the expression of odorant receptors (ORs) belonging to the superfamily of G-protein coupled receptors (GPCRs), as well as the canonical olfaction machinery (Golf and AC3) in the smooth muscle of human bronchi. In primary cultures of isolated human ASM, we identified mRNA expression for multiple ORs. Strikingly, OR51E2 was the most highly enriched OR transcript mapped to the human olfactome in lung-resident cells. In a heterologous expression system, OR51E2 trafficked readily to the cell surface and showed ligand selectivity and sensitivity to the short chain fatty acids (SCFAs) acetate and propionate. These endogenous metabolic byproducts of the gut microbiota slowed the rate of cytoskeletal remodeling, as well as the proliferation of human ASM cells. These cellular responses in vitro were found in ASM from non-asthmatics and asthmatics, and were absent in OR51E2-deleted primary human ASM. These results demonstrate a novel chemo-mechanical signaling network in the ASM and serve as a proof-of-concept that a specific receptor of the gut-lung axis can be targeted to treat airflow obstruction in asthma. |
| Databáze: | OpenAIRE |
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