Green tea polyphenol epigallocatechin-3-gallate suppresses rat hepatic stellate cell invasion by inh

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:xhbtbyrr
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Aim:Epigallocatechin-3-gallate(EGCG)is the major component of green teapolyphenols,whose wide range of biological properties includes anti-fibrogenicactivity.Matrix metalloproteinases(MMP)that participate in extracellular matrixdegradation are involved in the development of hepatic fibrosis.The presentstudy investigates whether EGCG inhibits activation of the major gelatinase matrixmetalloproteinase-2(MMP-2)in rat hepatic stellate cells(HSC).Methods:Theexpression of MMP-2,tissue inhibitors of metalloproteinases-2(TIMP-2),andmembrane-type 1-MMP(MT1-MMP)was assessed by RT-PCR and Western blotanalyses.MMP-2 activity was evaluated by zymography and MT1-MMP activitywas assessed by an enzymatic assay.HSC migration was measured by a woundhealing assay and cell invasion was performed using Transwell cell culturechambers.Results:The expression of MMP-2 mRNA and protein in HSC wassubstantially reduced by EGCG treatment.EGCG treatment also reduced con-canavalin A(ConA)-induced activation of secreted MMP-2 and reduced MT1-MMP activity in a dose-dependent manner.In addition,EGCG inhibited eitherHSC migration or invasion.Conclusion:The abilities of EGCG to suppress MMP-2 activation and HSC invasiveness suggest that EGCG may be useful in the treat-ment and prevention of hepatic fibrosis. Aim: Epigallocatechin-3-gallate (EGCG) is the major component of green teapolyphenols,whose wide range of biological properties includes anti-fibrogenic activity.Matrix metalloproteinases(MMP) that participate in extracellular matrix degradation is involved in the development of hepatic fibrosis.The presents are tudy Investigates whether EGCG inhibits activation of the major gelatinase matrixmetalloproteinase-2(MMP-2) in rat hepatic stellate cells(HSC).Methods:The expression of MMP-2,tissue inhibitors of metalloproteinases-2(TIMP-2),andmembrane-type 1 -MMP(MT1-MMP)was assessed by RT-PCR and Western blot analysis.MMP-2 activity was evaluated by zymography and MT1-MMP activitywas assessed by an enzymatic assay.HSC migration was measured by a woundhealing assay and cell invasion was performed using Transwell cell culture chambers.Results:The expression of MMP-2 mRNA and protein in HSC wassubstantially reduced by EGCG treatment.EGCG treatment reduced con-canavalin A(ConA)-induced activation of secre Ted MMP-2 and reduced MT1-MMP activity in a dose-dependent manner.In addition,EGCG inhibited either HSC migration or invasion.Conclusion:The abilities of EGCG to suppress MMP-2 activation and HSC invasiveness suggest that EGCG may be useful in the Treat-ment and prevention of hepatic fibrosis.
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