Departmental Papers (Dental)
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
Date of this Version
Journal of Investigative Dermatology
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.
Phosphatidylinositol 3-Kinase, 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
Zhang, Q., Paul, A. K., Wang, L., French, S. W., Tang, X., Duong, H. S., Messadi, D. V., & Le, A. D. (2006). 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. Journal of Investigative Dermatology, 126 (12), 2607-2613. http://dx.doi.org/10.1038/sj.jid.5700472
Date Posted: 10 February 2023
This document has been peer reviewed.
At the time of publication, author Qunzhao Zhang was affiliated with the University of Southern California, School of Dentistry. Currently, (s)he is a faculty member at the School of Medical Dentistry at the University of Pennsylvania.
At the time of publication, author Anh D. Le was affiliated with the University of Southern California, School of Dentistry. Currently, (s)he is a faculty member at the School of Medical Dentistry at the University of Pennsylvania.