Hung, Chi-FengHsiao, Chien-YuHsieh, Wen-HaoLi, Hsin-JuTsai, Yi-JuLin, Chun-NanChang, Hsun-HsienWu, Nan-Lin2017-11-212017Hung, Chi-Feng, Chien-Yu Hsiao, Wen-Hao Hsieh, Hsin-Ju Li, Yi-Ju Tsai, Chun-Nan Lin, Hsun-Hsien Chang, and Nan-Lin Wu. 2017. “18ß-glycyrrhetinic acid derivative promotes proliferation, migration and aquaporin-3 expression in human dermal fibroblasts.” PLoS ONE 12 (8): e0182981. doi:10.1371/journal.pone.0182981. http://dx.doi.org/10.1371/journal.pone.0182981.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34375113Licorice (Glycyrrhiza) species have been widely used as a traditional medicine and a natural sweetener in foods. The 18β-glycyrrhetinic acid (18β-GA) is a bioactive compound in licorice that exhibits potential anti-cancer, anti-inflammatory, and anti-microbial activities. Many synthesized derivatives of 18β-GA have been reported to be cytotoxic and suggested for the treatment of malignant diseases. In this study, we explored the possible pharmacological roles of an 18β-GA derivative in skin biology using primary human dermal fibroblasts and HaCaT keratinocytes as cell models. We found that this 18β-GA derivative did not cause cell death, but significantly enhanced the proliferation of dermal fibroblasts and HaCaT keratinocytes. A scratch wound healing assay revealed that the 18β-GA derivative promoted the migration of fibroblasts. Due to the important role of aquaporin-3 in cell migration and proliferation, we also investigated the expression of aquaporin-3 and found this compound up-regulated the expression of aquaporin-3 in dermal fibroblasts and HaCaT keratinocytes. In dermal fibroblasts, the 18β-GA derivative induced the phosphorylation of Akt, ERK, and p38. The inhibitor of Akt predominantly suppressed the 18β-GA derivative-induced expression of aquaporin-3. Collectively, this compound had a positive effect on the proliferation, migration, and aquaporin-3 expression of skin cells, implying its potential role in the treatment of skin diseases characterized by impaired wound healing or dermal defects.en-USBiology and Life SciencesCell BiologyCellular TypesAnimal CellsConnective Tissue CellsFibroblastsAnatomyBiological TissueConnective TissueMedicine and Health SciencesEpithelial CellsKeratinocytesEpitheliumPhysiologyPhysiological ProcessesTissue RepairWound HealingCell MotilityCell MigrationDevelopmental BiologyBioassays and physiological analysisBiochemical analysisColorimetric assaysMTT assayEnzyme assaysIntegumentary SystemSkinSkin PhysiologyDermatologySkin DiseasesCell ProcessesCell ProliferationJournal Article2017-11-2110.1371/journal.pone.0182981