Jeon, Yong Sic Kwon, Hyukjoon Ahn, Hong Ryul Huh, Gyuwon Kim, Taejung Park, Young Tae Park, Hyun Bong Jin-hyoung Jeong Jae-hyun Jo Kim, Young Joo Jung, Sang Hoon 2026-02-10T02:30:08Z 2026-02-10T02:30:08Z 2026-02-06 2026-02 1661-6596 https://pubs.kist.re.kr/handle/201004/154250 Dysregulated extracellular matrix (ECM) deposition and epithelial–mesenchymal transition (EMT) in the trabecular meshwork (TM) contribute to glaucoma-associated fibrotic remodeling, and lysophosphatidic acid (LPA) potently induces these profibrotic responses in human trabecular meshwork (HTM) cells. We investigated whether an ethanolic extract of Diospyros kaki leaves (EEDK) attenuates LPA-induced fibrosis and explored the underlying mechanisms. HTM cells were stimulated with LPA and treated with ethanol-based EEDK extracts. Expression of ECM/fibrosis-related genes (FN1, ACTA2, COL1A1, COL3A1, COL4A1, COL6A2, CCN2) and EMT markers (CDH2, VIM, SNAI1) was assessed, along with cell migration using a wound-healing assay. Upstream regulatory pathways were examined via transcription factor prediction, AP-1 reporter assays, and analyses of MAPK/AP-1 signaling. Among the extracts tested, the 70% ethanol EEDK extract showed the strongest antifibrotic activity, significantly reducing LPA-induced ECM gene/protein expression and inhibiting HTM cell migration in a dose-dependent manner, whereas the 90% ethanol extract showed minimal effects. LPA robustly activated MAPK-dependent AP-1 signaling, and either pharmacologic inhibition of MAPK pathways or treatment with 70% ethanol EEDK comparably suppressed AP-1 activity and decreased downstream ECM/EMT gene expression. Thus, 70% ethanol EEDK mitigates LPA-induced TM fibrosis by inhibiting MAPK/AP-1-mediated transcription, supporting its potential as an antifibrotic strategy for glaucoma. English Multidisciplinary Digital Publishing Institute (MDPI) Uncovering a Glaucoma-Linked Lysophosphatidic Acid–MAPK/AP-1 Fibrosis Axis in Human Trabecular Meshwork Cells and Its Modulation by Diospyros kaki Leaf Extract Article 10.3390/ijms27031544 1 International Journal of Molecular Sciences, v.27, no.3 International Journal of Molecular Sciences 27 3 N scie scopus 001687807400001 Biochemistry & Molecular Biology Chemistry, Multidisciplinary Biochemistry & Molecular Biology Chemistry Article INTRAOCULAR-PRESSURE REGULATION EXTRACELLULAR-MATRIX ACID PATHWAY EPITHELIAL-MESENCHYMAL TRANSITION glaucoma trabecular meshwork extracellular matrix MAPK signaling <italic>Diospyros kaki</italic>