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Tranexamic acid protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway.

Yanyan Lin·Yaling Wang·Wanjing Wang·Zhili Deng·Yiya Zhang·Yiran Peng·Jin Tang·Ji Li·Chuchu Huang·Dan Jian
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Abstract

BACKGROUND: Tranexamic acid (TXA) is widely used for pigmentary disorders, but its anti-ageing potential remains unclear. This study aimed to evaluate whether topical 3% TXA improves early periorbital wrinkles in women with facial melasma and to investigate whether TXA protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway. METHODS: Fifty women with melasma were randomized to 3% TXA serum plus moisturizer or moisturizer alone for 8 weeks, with follow-up to week 12. Periorbital wrinkles were graded using a modified Fitzpatrick Wrinkle Scale (MFWS). Separately, D-gal-induced senescence in HDFs was assessed via viability, SA-β-gal activity, senescence markers, ROS, antioxidant enzymes, SASP/ECM gene expression, and MAPK activation. GPR30 involvement was examined using antagonist G15, shRNA knockdown, and molecular docking. RESULTS: Topical TXA produced significantly greater MFWS reductions versus moisturizer alone at weeks 4, 8, and 12, with benefit persisting post-treatment. In HDFs, TXA preserved viability, reduced SA-β-gal positivity, attenuated p21/p16, restored Lamin B1, decreased ROS, and rescued antioxidant activities. TXA downregulated IL-6, IL-8, MMP1, and MMP3, and suppressed D-gal-induced ERK, JNK, and p38 phosphorylation. These effects were weakened by G15 or GPR30 knockdown; docking supported a stable TXA-GPR30 interaction. CONCLUSIONS: TXA showed clinical anti-wrinkle activity in melasma patients and protected HDFs from D-gal-induced senescence, partly via GPR30-dependent modulation of oxidative stress, SASP/ECM expression, and MAPK signalling. TXA is a promising candidate for skin ageing intervention.

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HumansFemaleFibroblastsReceptors, G-Protein-CoupledCellular SenescenceSkin AgingGalactoseTranexamic AcidMAP Kinase Signaling SystemAdultMiddle AgedCells, CulturedOxidative StressDermisSkinReactive Oxygen SpeciesReceptors, EstrogenGPR30MAPKTranexamic acidcellular senescenceoxidative stressskin ageingJournal ArticleRandomized Controlled TrialResearch Support, Non-U.S. Gov't

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Yanyan Lin, Yaling Wang, Wanjing Wang, Zhili Deng, Yiya Zhang, Yiran Peng, Jin Tang, Ji Li, Chuchu Huang, Dan Jian. 2026-04-30. Tranexamic acid protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway.. https://doi.org/10.1080/07853890.2026.2663263

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Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't resourceAdult subjectCells, Cultured subjectCellular Senescence subjectDermis subjectFemale subjectFibroblasts subjectGPR30 subjectGalactose subjectHumans subjectJournal Article subjectMAP Kinase Signaling System subjectMAPK subjectMiddle Aged subjectOxidative Stress subjectRandomized controlled trials study

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