PMID- 16841034 OWN - NLM STAT- MEDLINE DCOM- 20061214 LR - 20220311 IS - 1523-1747 (Electronic) IS - 0022-202X (Linking) VI - 126 IP - 12 DP - 2006 Dec TI - 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. PG - 2607-13 AB - 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. FAU - Zhang, Qunzhou AU - Zhang Q AD - Center for Craniofacial Molecular Biology, University of Southern California, School of Dentistry, Los Angeles, California 90033, USA. FAU - Kelly, A Paul AU - Kelly AP FAU - Wang, Lina AU - Wang L FAU - French, Samuel W AU - French SW FAU - Tang, Xudong AU - Tang X FAU - Duong, Hai S AU - Duong HS FAU - Messadi, Diana V AU - Messadi DV FAU - Le, Anh D AU - Le AD LA - eng GR - S11 AR47359/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20060713 PL - United States TA - J Invest Dermatol JT - The Journal of investigative dermatology JID - 0426720 RN - 0 (Collagen Type I) RN - 0 (Plant Extracts) RN - 8R1V1STN48 (Catechin) RN - BQM438CTEL (epigallocatechin gallate) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Camellia sinensis/*chemistry MH - Catechin/*analogs & derivatives/pharmacology MH - Cells, Cultured MH - Coculture Techniques MH - Collagen Type I/*metabolism MH - Fibroblasts/*metabolism MH - Humans MH - Keloid/*metabolism/pathology MH - Mast Cells/*physiology MH - Phosphatidylinositol 3-Kinases/metabolism MH - Plant Extracts/*pharmacology MH - Proto-Oncogene Proteins c-akt/metabolism MH - Signal Transduction/drug effects EDAT- 2006/07/15 09:00 MHDA- 2006/12/15 09:00 CRDT- 2006/07/15 09:00 PHST- 2006/07/15 09:00 [pubmed] PHST- 2006/12/15 09:00 [medline] PHST- 2006/07/15 09:00 [entrez] AID - S0022-202X(15)32708-1 [pii] AID - 10.1038/sj.jid.5700472 [doi] PST - ppublish SO - J Invest Dermatol. 2006 Dec;126(12):2607-13. doi: 10.1038/sj.jid.5700472. Epub 2006 Jul 13.