Zhang, QunzhouPaul, A KellyWang, LinaFrench, Samuel WTang, XudongDuong, Hai SMessadi, Diana VLe, Anh D2023-05-222023-05-222006-12-012022-06-23https://repository.upenn.edu/handle/20.500.14332/9279Keloid, a chronic fibro-proliferative disease, exhibits distinctive histological features characterized by an abundant extracellular matrix stroma, a local infiltration of inflammatory cells including mast cells (MCs), and a milieu of enriched cytokines. Previous studies have demonstrated that co-culture with MCs stimulate type I collagen synthesis in fibroblasts, but the signaling mechanisms remain largely unknown. In this study, we investigated the signaling pathways involved in MC-stimulated type I collagen synthesis and the effects of green tea extract (GTE) and its major catechin, (-)-epigallocatechin-3-gallate (EGCG), on collagen homeostasis in keloid fibroblasts. Our results showed that MCs significantly stimulated type I collagen expression in keloid fibroblasts, and the upregulation of type I collagen was significantly attenuated by blockade of phosphatidylinositol-3-kinase (PI-3K), mammalian target of rapamycin (mTOR), and p38 MAPK signaling pathways, but not by blockade of ERK1/2 pathway. Furthermore, GTE and EGCG dramatically inhibited type I collagen production possibly by interfering with the PI-3K/Akt/mTOR signaling pathway. Our findings suggest that interaction between MCs and keloid fibroblasts may contribute to excessive collagen accumulation in keloids and imply a therapeutic potential of green tea for the intervention and prevention of keloids and other fibrotic diseases. © 2006 The Society for Investigative Dermatology.Phosphatidylinositol 3-KinaseCamellia sinensisCatechinCellsCulturedCoculture TechniquesCollagen Type IFibroblastsHumansKeloidMast CellsPlant ExtractsProto-Oncogene Proteins c-aktSignal Transductioncollagen type 1epigallocatechin gallategreen tea extractmammalian target of rapamycinmitogen activated protein kinase 1mitogen activated protein kinase 3mitogen activated protein kinase p38phosphatidylinositol 3 kinaseprotein kinase Barticlecell stimulationcollagen synthesiscontrolled studydrug effectfibroblasthomeostasishumanhuman cellhuman tissuekeloidmast cellpriority journalprotein expressionsignal transductionupregulationDentistryArticle