Green tea polyphenol epigallocatechin-3-gallate suppresses rat hepatic stellate cell invasion by inhibition of MMP-2 expression and its activation.
OBJECTIVE
Epigallocatechin-3-gallate (EGCG) is the major component of green tea polyphenols, whose wide range of biological properties includes anti-fibrogenic activity. Matrix metalloproteinases (MMP) that participate in extracellular matrix degradation are involved in the development of hepatic fibrosis. The present study investigates whether EGCG inhibits activation of the major gelatinase matrix metalloproteinase-2 (MMP-2) in rat hepatic stellate cells (HSC).


METHODS
The expression of MMP-2, tissue inhibitors of metalloproteinases-2 (TIMP-2), and membrane-type 1-MMP (MT1-MMP) was assessed by RT-PCR and Western blot analyses. MMP-2 activity was evaluated by zymography and MT1-MMP activity was assessed by an enzymatic assay. HSC migration was measured by a wound healing assay and cell invasion was performed using Transwell cell culture chambers.


RESULTS
The expression of MMP-2 mRNA and protein in HSC was substantially reduced by EGCG treatment. EGCG treatment also reduced concanavalin A (ConA)-induced activation of secreted MMP-2 and reduced MT1-MMP activity in a dose-dependent manner. In addition, EGCG inhibited either HSC migration or invasion.


CONCLUSIONS
The abilities of EGCG to suppress MMP-2 activation and HSC invasiveness suggest that EGCG may be useful in the treatment and prevention of hepatic fibrosis.
Zhen
Mao-chuan
MC
Department of Hepatobiliary Surgery, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
Huang
Xiao-hui
XH
Wang
Qian
Q
Sun
Kai
K
Liu
Yun-jian
YJ
Li
Wen
W
Zhang
Long-juan
LJ
Cao
Liang-qi
LQ
Chen
Xi-ling
XL
D000818:Animals; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000096:biosynthesis / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D013662:Tea / Q000737:chemistry
D012333:RNA, Messenger; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D053511:Matrix Metalloproteinase 14