Role of GPR40/120 omega‐3 fatty acid receptors on barrier function of airway epithelial cells

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The airway epithelium serves as a physical barrier, whose integrity is maintained by tight junctions. Disruption of epithelial barrier function leads to increased permeability of harmful particles and pathogens, causing the development of various airway diseases. G protein‐coupled receptor 40 (GPR40) and G protein‐coupled receptor 120 (GPR120) have been discovered as receptors of omega‐3 fatty acids, and activation of these receptors induces AMP‐activated protein kinase (AMPK) activation, which is known to promote tight junction assembly. This study aimed to investigate the effect of omega‐3 fatty acid receptors, namely GPR40 and GPR120, on tight junction integrity of airway epithelial cells (Calu‐3 cells). Cell junctional assembly was measured by calcium switch assays and transepithelial electrical resistance (TER) analyses. We found that GW9508, an agonist of GPR40/120, promoted tight junction assembly of airway epithelial cells. This effect was abolished by specific antagonists of GPR40 and GPR120. In addition, the enhancement of airway barrier function by GPR40/120 agonist was mediated via a phospholipase C‐ calcium/calmodulin‐dependent protein kinase kinase (CaMKK)‐AMPK pathway. Taken together, these results indicate that activation of GPR40/120 has a beneficial effect in promoting airway epithelial barrier integrity and may be of therapeutic potential in airway diseases resulting from airway epithelial disruption including chronic obstructive pulmonary disease.Support or Funding InformationThis work was supported by Thailand Research Fund and Mahidol University (Grant BRG5980008), Faculty of Science, Mahidol University, and Faculty of Medicine Ramathibodi Hospital, Mahidol University (Tonkla Ramathibodi Project).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.