Open AccessSuppressive effect of epigallocatechin‐3‐O‐gallate on endoglin molecular regulation in myocardial fibrosis in vitro and in vivo
Author(s) -
Lin ChiuMei,
Chang Hang,
Wang BaoWei,
Shyu KouGi
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12895
Subject(s) - endoglin , in vivo , chemistry , blot , myocardial fibrosis , kinase , microbiology and biotechnology , p38 mitogen activated protein kinases , electrophoretic mobility shift assay , fibrosis , extracellular , in vitro , medicine , protein kinase a , gene expression , biology , biochemistry , stem cell , cd34 , gene
Epigallocatechin‐3‐O‐gallate ( EGCG ), derived from green tea, has been studied extensively because of its diverse physiological and pharmacological properties. This study evaluates the protective effect of EGCG on angiotensin II (Ang II )‐induced endoglin expression in vitro and in vivo . Cardiac fibroblasts ( CF s) from the thoracic aorta of adult Wistar rats were cultured and induced with Ang II . Western blotting, Northern blotting, real‐time PCR and promoter activity assay were performed. Ang II increased endoglin expression significantly as compared with control cells. The specific extracellular signal‐regulated kinase inhibitor SP 600125 ( JNK inhibitor), EGCG (100 μM) and c‐Jun N‐terminal kinase ( JNK ) si RNA attenuated endoglin proteins following Ang II induction. In addition, pre‐treated Ang II ‐induced endoglin with EGCG diminished the binding activity of AP ‐1 by electrophoretic mobility shift assay. Moreover, the luciferase assay results revealed that EGCG suppressed the endoglin promoter activity in Ang II ‐induced CF s by AP ‐1 binding. Finally, EGCG and the JNK inhibitor ( SP 600125) were found to have attenuated endoglin expression significantly in Ang II ‐induced CF s, as determined through confocal microscopy. Following in vivo acute myocardial infarction ( AMI )‐related myocardial fibrosis study, as well as immunohistochemical and confocal analyses, after treatment with endoglin si RNA and EGCG (50 mg/kg), the area of myocardial fibrosis reduced by 53.4% and 64.5% and attenuated the left ventricular end‐diastolic and systolic dimensions, and friction shortening in hemodynamic monitor. In conclusion, epigallocatechin‐3‐O‐gallate ( EGCG ) attenuated the endoglin expression and myocardial fibrosis by anti‐inflammatory effect in vitro and in vivo , the novel suppressive effect was mediated through JNK / AP ‐1 pathway.