Green Tea Extract and (−)-Epigallocatechin-3-Gallate Inhibit Mast Cell-Stimulated Type I Collagen Expression in Keloid Fibroblasts via Blocking PI-3K/Akt Signaling Pathways
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Camellia sinensis
Catechin
Cells
Cultured
Coculture Techniques
Collagen Type I
Fibroblasts
Humans
Keloid
Mast Cells
Plant Extracts
Proto-Oncogene Proteins c-akt
Signal Transduction
collagen type 1
epigallocatechin gallate
green tea extract
mammalian target of rapamycin
mitogen activated protein kinase 1
mitogen activated protein kinase 3
mitogen activated protein kinase p38
phosphatidylinositol 3 kinase
protein kinase B
article
cell stimulation
collagen synthesis
controlled study
drug effect
fibroblast
homeostasis
human
human cell
human tissue
keloid
mast cell
priority journal
protein expression
signal transduction
upregulation
Dentistry
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Abstract
Keloid, 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.