北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学第三临床医学院  > 期刊论文
学科主题: 临床医学
题名:
Up-Regulating Relaxin Expression by G-Quadruplex Interactive Ligand to Achieve Antifibrotic Action
作者: 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
发表日期: 2012-08-01
DOI: 10.1210/en.2012-1114
卷: 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
所属项目编号: 90913004 ; 81070196 ; 81030001 ; 20100001110101 ; APP1004235
项目资助者: 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
WOS记录号: WOS:000306652400017
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53022
Appears in Collections:北京大学第三临床医学院_期刊论文

Files in This Item:

There are no files associated with this item.


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

Recommended Citation:
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.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Gu, Hui-Ping]'s Articles
[Lin, Sen]'s Articles
[Xu, Ming]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Gu, Hui-Ping]‘s Articles
[Lin, Sen]‘s Articles
[Xu, Ming]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2018  北京大学医学部 - Feedback
Powered by CSpace