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Sung-Gu Park,1,* Il-Joo Jo,2,* Seol-A Park,3 Min-Cheol Park,1 Yeun-Ja Mun4 1Department of Oriental Medical Ophthalmology & Otolaryngology & Dermatology, College of Korean Medicine, Wonkwang University, Iksan, South Korea; 2Central Stroke Center of Korean medicine, College of Korean Medicine, Wonkwang University, Iksan, South Korea; 3Department of Beauty Design Graduate School, Wonkwang University, Iksan, South Korea; 4Department of Anatomy, College of Korean Medicine, Wonkwang University, Iksan, South Korea*These authors contributed equally to this workCorrespondence: Yeun-Ja Mun, Department of Anatomy, College of Korean Medicine, Wonkwang University, Iksan, South Korea, Tel +82-63-850-6942, Email yjmun@wku.ac.krBackground: Poria cocos (PC), a fungus, has been used for more than 2000 years as a food and medicine in China. PC and its components have various pharmacological effects on the skin, including immunomodulatory activities, barrier function improvement, and anti-tumor effects. However, the effect of PC in aquaporin-3 (AQP3) expression, which is essential for epidermal water permeability barrier maintenance, was not reported.Methods: This study examined the mechanism through which the ethanol extract of the sclerotium of PC (EPC) promoted the expression of AQP3 in cultured human keratinocytes. Western blotting was used to investigate the expression of AQPs and the activation of phosphoinositide 3-kinase (PI3K)/Akt-related signaling molecules in HaCaT cells. Cells were treated with inhibitors of PI3K/Akt and mechanistic target of rapamycin (mTOR) prior to EPC treatment.Results: EPC promoted the expression of AQP3 in HaCaT cells without affecting AQP1 and AQP2 expression. Phosphorylated Akt levels were increased by EPC treatment, and the inhibition of PI3K by LY2940002 resulted in a reduction in EPC-induced AQP3 expression. Furthermore, EPC stimulated the phosphorylation of p70S6K and AktSer473, which are downstream targets of mTO