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GPR40 receptor activation promotes tight junction assembly in airway epithelial cells via AMPK-dependent mechanisms.


ABSTRACT: 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 Ca2+ measurements confirmed that GW9508 stimulated GPR40, but not GPR120. In Ca2+ 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 ? (CaMKK?). Collectively, this study reveals an unprecedented role of GPR40 in facilitating airway epithelial tight junction assembly via PLC-CaMKK?-AMPK pathways. GPR40 represents a novel regulator of airway epithelial integrity and its stimulation may be beneficial in the treatment of airway diseases.

SUBMITTER: Moonwiriyakit A 

PROVIDER: S-EPMC6179133 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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GPR40 receptor activation promotes tight junction assembly in airway epithelial cells via AMPK-dependent mechanisms.

Moonwiriyakit Aekkacha A   Wattanaphichet Panisara P   Chatsudthipong Varanuj V   Muanprasat Chatchai C  

Tissue barriers 20180829 2


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 ce  ...[more]

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