Publication: GPR40 receptor activation promotes tight junction assembly in airway epithelial cells via AMPK-dependent mechanisms
Issued Date
2018-04-03
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ISSN
21688370
21688362
21688362
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2-s2.0-85053029607
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Mahidol University
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SCOPUS
Bibliographic Citation
Tissue Barriers. Vol.6, No.2 (2018), 1-12
Suggested Citation
Aekkacha Moonwiriyakit, Panisara Wattanaphichet, Varanuj Chatsudthipong, Chatchai Muanprasat GPR40 receptor activation promotes tight junction assembly in airway epithelial cells via AMPK-dependent mechanisms. Tissue Barriers. Vol.6, No.2 (2018), 1-12. doi:10.1080/21688370.2018.1480741 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/45188
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Title
GPR40 receptor activation promotes tight junction assembly in airway epithelial cells via AMPK-dependent mechanisms
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Abstract
© 2018, © 2018 Taylor & Francis. Tight junctions play key roles in the regulation of airway epithelial barrier function and promotion of tight junction integrity is beneficial to lung health. G-protein coupled receptor (GPR) 40 has been identified as a receptor of polyunsaturated fatty acids. This study aimed to investigate the function of GPR40 in regulating tight junction assembly in human airway epithelial cells (Calu-3 cells) using GW9508, a GPR40 agonist. Immunoblotting and immunofluorescence analyses showed that Calu-3 cells expressed both types of polyunsaturated fatty acid receptors including GPR40 and GPR120. Intracellular Ca 2+ measurements confirmed that GW9508 stimulated GPR40, but not GPR120. In Ca 2+ switch assays, GW9508 promoted the recovery of transepithelial electrical resistance and re-localization of zonula occludens (ZO)-1 to intercellular areas. These effects were suppressed by inhibitors of GPR40 and phospholipase C (PLC). Interestingly, GW9508 enhanced tight junction assembly in an AMP-activated protein kinase (AMPK)-dependent manner. The effect of GW9508 on inducing tight junction assembly was also confirmed in 16HBE14o- cells. Our results indicate that GPR40 stimulation by GW9508 leads to AMPK activation via calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ). Collectively, this study reveals an unprecedented role of GPR40 in facilitating airway epithelial tight junction assembly via PLC-CaMKKβ-AMPK pathways. GPR40 represents a novel regulator of airway epithelial integrity and its stimulation may be beneficial in the treatment of airway diseases.