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Up-Regulating Relaxin Expression by G-Quadruplex Interactive Ligand to Achieve Antifibrotic Action
Gu, Hui-Ping1,2,3; Lin, Sen4; Xu, Ming1,2,3; Yu, Hai-Yi1,2,3; Du, Xiao-Jun5; Zhang, You-Yi1,2,3; Yuan, Gu4; Gao, Wei1,2,3
刊名ENDOCRINOLOGY
2012-08-01
DOI10.1210/en.2012-1114
153期:8页:3692-3700
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Endocrinology & Metabolism
研究领域[WOS]Endocrinology & Metabolism
关键词[WOS]SPONTANEOUSLY HYPERTENSIVE-RATS ; CARDIAC FIBROBLASTS ; BERBERINE DERIVATIVES ; CIRCULAR-DICHROISM ; ANGIOTENSIN-II ; HEART-FAILURE ; HUMAN GENOME ; FIBROSIS ; GENE ; CELLS
英文摘要

Myocardial fibrosis is a key pathological change in a variety of heart diseases contributing to the development of heart failure, arrhythmias, and sudden death. Recent studies have shown that relaxin prevents and reverses cardiac fibrosis. Endogenous expression of relaxin was elevated in the setting of heart disease; the extent of such up-regulation, however, is insufficient to exert compensatory actions, and the mechanism regulating relaxin expression is poorly defined. In the rat relaxin-1 (RLN1, Chr1) gene promoter region we found presence of repeated guanine (G)-rich sequences, which allowed formation and stabilization of G-quadruplexes with the addition of a G-quadruplex interactive ligand berberine. The G-rich sequences and the G-quadruplexes were localized adjacent to the binding motif of signal transducer and activator of transcription (STAT) 3, which negatively regulates relaxin expression. Thus, we hypothesized that the formation and stabilization of G-quadruplexes by berberine could influence relaxin expression. We found that berberine-induced formation of G-quadruplexes did increase relaxin gene expression measured at mRNA and protein levels. Formation of G-quadruplexes significantly reduced STAT3 binding to the promoter of relaxin gene. This was associated with consequent increase in the binding of RNA polymerase II and STAT5a to relaxin gene promoter. In cardiac fibroblasts and rats treated with angiotensin II, berberine was found to suppress fibroblast activation, collagen synthesis, and extent of cardiac fibrosis through up-regulating relaxin. The antifibrotic action of berberine in vitro and in vivo was similar to that by exogenous relaxin. Our findings document a novel therapeutic strategy for fibrosis through up-regulating expression of endogenous relaxin. (Endocrinology 153: 3692-3700, 2012)

语种英语
WOS记录号WOS:000306652400017
项目编号90913004 ; 81070196 ; 81030001 ; 20100001110101 ; APP1004235
资助机构National Natural Science Foundation of China ; Program for New Century Excellent Talents in University ; Beijing Talents Foundation ; Ph.D. Programs Foundation of Ministry of Education of China ; National Health and Medical Research Council of Australia
引用统计
被引频次:21[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/53022
专题北京大学第三临床医学院
北京大学第三临床医学院_心血管内科
作者单位1.Peking Univ, Minist Hlth, Hosp 3, Key Lab Mol Cardiovasc Mol Biol & Regulatory Pept, Beijing 100871, Peoples R China
2.Peking Univ, Minist Educ, Inst Vasc Med, Beijing 100871, Peoples R China
3.Peking Univ, Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100871, Peoples R China
4.Peking Univ, Dept Biol Chem, Natl Lab Mol Sci,Coll Chem & Mol Engn, Key Lab Bioorgan Chem & Mol Engn,Minist Educ, Beijing 100871, Peoples R China
5.Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia
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GB/T 7714
Gu, Hui-Ping,Lin, Sen,Xu, Ming,et al. Up-Regulating Relaxin Expression by G-Quadruplex Interactive Ligand to Achieve Antifibrotic Action[J]. ENDOCRINOLOGY,2012,153(8):3692-3700.
APA Gu, Hui-Ping.,Lin, Sen.,Xu, Ming.,Yu, Hai-Yi.,Du, Xiao-Jun.,...&Gao, Wei.(2012).Up-Regulating Relaxin Expression by G-Quadruplex Interactive Ligand to Achieve Antifibrotic Action.ENDOCRINOLOGY,153(8),3692-3700.
MLA Gu, Hui-Ping,et al."Up-Regulating Relaxin Expression by G-Quadruplex Interactive Ligand to Achieve Antifibrotic Action".ENDOCRINOLOGY 153.8(2012):3692-3700.
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