Roles of GPR39 in Regulating Keratinocyte Proliferation and Inflammation

Zinc is an important trace element that plays key roles in the human body. Previous reports showed that zinc supplement could relieve dermatitis and improve wound healing process with unknown molecular target. In this study, we investigated the roles of G‐protein coupled receptor 39 (GPR39), a zinc‐sensing receptor, on keratinocyte proliferation and inflammation using a GPR39 agonist TC‐G 1008. Immortalized human keratinocyte cell line (HaCaT cells) was used as an in vitro model. We first verified protein expression and function of GPR39 in HaCaT cells by Western blot and Indo‐1 calcium flux assays. Importantly, at 48 h post‐treatment, Bromodeoxyuridine (BrdU) incorporation assay showed that TC‐G 1008 significantly increased keratinocyte proliferation in a concentration‐dependent manner with a maximal effect being observed at 1 μM. Moreover, TC‐G 1008 enhanced mammalian target of rapamycin (mTOR) phosphorylation in a time‐dependent manner, indicating that GPR39 activation led to keratinocyte proliferation. Next, immunofluorescence staining demonstrated that TC‐G 1008 significantly reduced tumor necrosis factor‐alpha (TNF‐α)‐induced nuclear factor‐kappa B (NF‐κB) nuclear translocation. Interestingly, this effect was abolished by co‐treatment with compound C, AMP‐activated protein kinase (AMPK) inhibitor. These results supported that GPR39 activation promotes wound healing and exerts anti‐inflammatory effect in human keratinocytes, at least in part, by stimulating mTOR and AMPK, respectively. Support or Funding Information This work was supported by Thailand Research Fund and Mahidol University (BRG5980008), Faculty of Science, Mahidol University and the Medical Scholars Program (Ph.D.‐M.D. program), Mahidol University. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .