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|本期目录/Table of Contents|

血管紧张素II对心脏成纤维细胞Ets-1表达的影响及机制研究

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2016年第3期
页码:
253-257,284
栏目:
基础研究
出版日期:
2016-01-05

文章信息/Info

Title:
Regulation of angiotensin II in Ets-1 expression and its mechanism in cardiac fibroblasts
作者:
郝广华; 牛小麟; 韩振华; 魏 瑾; 高登峰
（西安交通大学医学院第二附属医院心内科，陕西 西安 710004）
Author(s):
HAO Guang-hua;  Niu Xiao-lin;  HAN Zhen-hua;  WEI Jin;  GAO Deng-feng
(Department of Cardiology, Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710004, Shaanxi, China)
关键词:
血管紧张素II; 成纤维细胞; Ets-1; 结缔组织生长因子; 纤溶酶原激活物抑制因子-1
Keywords:
angiotensin;  fibroblast;  Ets-1;  connective tissue growth factor;  plasminogen activator inhibitor-1
分类号:
R542.2
DOI:
-
文献标识码:
A
摘要:
目的 研究血管紧张素II（AngII）对大鼠心脏成纤维细胞(CFs)转录因子Ets-1及其下游促纤维化因子表达和细胞增殖的调节及相关的分子机制。方法 将原代培养的大鼠CFs分为对照组，AngII处理不同时间组以及不同剂量组，采用实时定量RT-PCR及western blotting实验技术检测AngII对Ets-1mRNA及蛋白表达的影响。用AngII受体拮抗剂、MAPKs、PKC及PTK抑制剂预处理CFs，测定其对AngII诱导的Ets-1、结缔组织生长因子(CTGF)、纤溶酶原激活物抑制因子-1(PAI-1)表达及细胞增殖的影响。结果 在CFs中，AngII可呈时间及浓度依赖性诱导Ets-1表达(P<0.05)，对其mRNA稳定性则无显著影响。血管紧张素II1型受体(AT1R)拮抗剂losartan、ERK抑制剂PD98059、JNK抑制剂SP600125及PKC抑制剂BIM预处理可显著抑制AngII诱导Ets-1过表达(P<0.05)，下调CTGF及PAI-1蛋白表达，抑制AngII诱导的CFs增殖(P<0.05)。结论 AngII通过AT1R及PKC,ERK、JNK信号通路介导诱导CFs Ets-1基因的表达。而且，转录因子Ets-1可能是心肌纤维化过程的一个重要介导因素，其发挥作用的主要途径可能是通过参与调控CFs增殖及促纤维化因子CTGF及PAI-1的表达。
Abstract:
AIM To investigate the role of Ets-1 in profibrotic actions of angiotensin II (AngII) in cardiac fibroblasts (CFs). METHODS Primary cultured CFs were divided into the following groups: control, AngII treated for different time and different dose. Expression levels of Ets-1 mRNA and protein were examined using real-time RT-PCR and Western blotting. CFs were pretreated with AngII receptor blocker, inhibitors of MAPKs, PKC, and PTK. AngII-induced cell proliferation and expression of Ets-1. Connective tissue growth factor (CTGF) and plasminogen activator inhibitor-1 (PAI-1) were examined using MTT, real-time RT-PCR and Western blotting. RESULTS In growth-arrested CFs, AngII induced Ets-1 expression in a time- and concentration-dependent manner (P<0.05). Pretreatment with AngII type 1 receptor (AT1R) blocker losartan, PKC inhibitor BIM, ERK inhibitor PD98059, or JNK inhibitor SP600125 partly inhibited this induction (P<0.05) accompanied by impaired cell proliferation and production of PAI-1 and CTGF protein (P<0.05), the two downstream targets of Ets-1. CONCLUSION AngII induces Ets-1 expression through AT1R and PKC, ERK and JNK signaling pathways. Ets-1 may be an important mediator in cardiac fibrosis process by regulating CF proliferation and expression of CTGF and PAI-1.

参考文献/References

[1]Leask A.Getting to the heart of the matter:new insights into cardiac fibrosis[J].Circ Res,2015,116(7):1269-1276.
[2]Di J,Jiang L,Zhou Y,et al.Ets-1 targeted by microrna-221 regulates angiotensin II-induced renal fibroblast activation and fibrosis[J].Cell Physiol Biochem,2014,34(4):1063-1074.
[3]Chen CC,Ferreri NR.Epithelium-specific ETS-1:a counter-regulatory factor against vascular dysfunction and inflammation[J].Am J Hypertens,2010,23(12):1252.
[4]Mouly E,Chemin K,Nguyen HV,et al.The Ets-1 transcription factor controls the development and function of natural regulatory T cells[J].J Exp Med,2010,207(10):2113-2125.
[5]Kurdi M,Booz GW.New take on the role of angiotensin II in cardiac hypertrophy and fibrosis[J].Hypertension,2011,57(6):1034-1038.
[6]Tao H,Yang JJ,Shi KH,et al.DNA methylation in cardiac fibrosis: new advances and perspectives[J].Toxicology,2014,323:125-129.
[7]Liu MY,Eyries M,Zhang C,et al.Inducible platelet-derived growth factor D-chain expression by angiotensin II and hydrogen peroxide involves transcriptional regulation by Ets-1 and Sp1[J].Blood,2006,107(6):2322-2329.
[8]Watanabe D,Takagi H,Suzuma K,et al.Transcription factor Ets-1 mediates ischemia- and vascular endothelial growth factor-dependent retinal neovascularization[J].Am J Pathol,2004,164(5):1827-1835.
[9]Goetze S,Kintscher U,Kaneshiro K,et al.TNFalpha induces expression of transcription factors c-fos,Egr-1,and Ets-1 in vascular lesions through extracellular signal-regulated kinases 1/2[J].Atherosclerosis,2001,159(1):93-101.
[10]Taniguchi H,Fujiwara Y,Doki Y,et al.Gene therapy using ets-1 transcription factor decoy for peritoneal dissemination of gastric cancer[J].Int J Cancer,2007,121(7):1609-1617.
[11]Simon DI,Simon NM.Plasminogen activator inhibitor-1:a novel therapeutic target for hypertension?[J].Circulation,2013,128(21):2286-2288.
[12]Zhan Y,Brown C,Maynard E,et al.Ets-1 is a critical regulator of Ang II-mediated vascular inflammation and remodeling[J].J Clin Invest,2005,115(9):2508-2516.
[13]Daniels A,van Bilsen M,Goldschmeding R,et al.Connective tissue growth factor and cardiac fibrosis[J].Acta Physiol(Oxf)2009,195(3):321-338.
[14]Nakerakanti SS,Kapanadze B,Yamasaki M,et al.Fli1 and Ets1 have distinct roles in connective tissue growth factor/CCN2 gene regulation and induction of the profibrotic gene program[J].J Biol Chem,2006,281(35):25259-25269.

备注/Memo

备注/Memo:
收稿日期：2015-07-17.
基金项目：国家自然科学基金项目资助（30900693）
通讯作者：牛小麟，教授，主要从事心血管病理生理及药理学研究 Email：niuxl@mail.xjtu.edu.cn
作者简介：郝广华，主治医师 Email:guanghua-h@163.com
更新日期/Last Update: 2016-01-07