Abstract
Zinc deficiency is associated with several gastrointestinal diseases such as diarrhea and IBD, whose pathogenesis is partly due to impaired intestinal barrier function. This observation suggests the beneficial role of zinc in regulating intestinal barrier function. The aim of this study was to investigate the effect of GPR39, a zinc‐sensing receptor, on intestinal barrier function and its underlying mechanisms. The results showed that treatment of T84 cell monolayers with TC‐G 1008, a GPR39 agonist significantly increased their transepithelial electrical resistance (TEER), indicating increased intestinal barrier function. The TC‐G 1008‐induced increase in TEER was in a time‐ and dose‐dependent manner. Moreover, co‐treatment with compound C, an AMPK inhibitor, completely abolished the effect of GPR39 agonist on TEER. This result suggests that AMPK may mediate the action of GPR39 agonist. In support of this notion, western blot analysis demonstrated that TC‐G 1008 time‐dependently induced AMPK phosphorylation, which reached its maximum at 2 hours paralleling the change in TER. Taken together, our results indicate that GPR39 activation can improve intestinal barrier function through an AMPK‐dependent pathway. This study provides an insight into the roles of GPR39 in the control of intestinal epithelial barrier integrity, which may be important for understanding pathogenesis or developing treatment of intestinal diseases.Support or Funding InformationThis work was supported by grants BRG5980008 from Thailand Research Fund and Mahidol University and Tonkla Ramathibodi Project from Faculty of Medicine Ramathibodi Hospital, Mahidol University.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Published Version
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