Green tea polyphenol epigallocatechin-3-gallate inhihits platelet-derived growth factor-induced proliferation of human hepatic stellate cell line LI90

Background Aims: Green-tea polyphenols are known to have anti-fibrotic properties of the skin and the artery. The proliferation of hepatic stellate cells (HSC) is closely related to the progression of liver fibrosis in chronic liver diseases. We investigated the inhibitory effect of epigallocatechin-3-gallate (EGCG), the major potential inhibitory component of green-tea polyphenols, on the proliferation of HSC. The aim of this study was to clarify the molecular mechanisms of EGCG inhibition of HSC proliferation. Methods: A cultured human hepatic stellate cell line L190 was used for this study. The cells were stimulated by platelet-derived growth factor (PDGF)-BB in the presence or absence of EGCG. Proliferation was determined by bromodeoxy-uridine incorporation. The mRNA expressions of collagen alpha1(I) and (IV) were evaluated by a quantitative reverse transcription-polymerase chain reaction. PDGF receptor tyrosine phosphorylation was detected using anti-phosphotyrosine antibody. PDGF receptor radioligand binding assay was performed by [I-125]-PDGF-BB. Results: EGCG inhibited the PDGF-BB-induced cell-proliferation and collagen alpha1(I) and (IV) mRNA expressions. EGCG reduced the autophosphorylation of the PDGF receptor. EGCG blocked PDGF-BB binding to its receptor in a non-competitive manner. Conclusions: EGCG has an inhibitory effect on PDGF-induced proliferation of HSC, and the blocking of PDGF-BB binding to its receptor may be the mechanism behind this effect. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.