我们的网站为什么显示成这样?

可能因为您的浏览器不支持样式,您可以更新您的浏览器到最新版本,以获取对此功能的支持,访问下面的网站,获取关于浏览器的信息:

|本期目录/Table of Contents|

miR-148b参与心肌梗死后心脏纤维化的作用及机制(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2017年第2期
页码:
149-153
栏目:
基础研究
出版日期:
2016-11-25

文章信息/Info

Title:
Role and mechanism of miR-148b involved in cardiac fibrosis after myocardial infarction
作者:
赵 娜1李 娜2刘小军1徐姣姣1夏东雨1牛小麟3刘仲伟1
(1.陕西省人民医院心内一科,陕西 西安 710068;
西安交通大学:2.第一附属医院心内科,陕西 西安 710061,3.第二附属医院心内科,陕西 西安 710004)
Author(s):
ZHAO Na1 LI Na2 LIU Xiao-jun1 XU Jiao-jiao1 XIA Dong-yu1 NIU Xiao-lin3 LIU Zhong-wei1
(1.Department of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi, China;
2.Department of Cardiology, First Affiliated Hospital, Medical College, Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China;
3.Department of Cardiology, Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710004, Shaanxi, China)
关键词:
心肌梗死心脏纤维化miR-148bPTEN
Keywords:
myocardial infarction cardiac fibrosis miR-148b PTEN
分类号:
R734.2
DOI:
-
文献标识码:
A
摘要:
目的 探讨miR-148b参与大鼠心肌梗死后心脏纤维化的作用及可能机制。方法 采用结扎大鼠冠状动脉左前降支方法制作大鼠心肌梗死模型,RT-PCR法评价大鼠心脏miR-148b表达水平;应用生物信息学方法预测miR-148b靶基因;采用Western blot方法评价大鼠心脏同源性磷酸酶-张力蛋白(phosphatase and tensin homologue,PTEN)及α-平滑肌蛋白(α-smooth muscle actin,α-SMA)蛋白表达水平;四甲基偶氮唑盐比色(MTT)法检测心脏成纤维细胞增殖能力;应用天狼猩红染色评价心脏纤维化病理改变。结果 大鼠心肌梗死组,梗死周边区纤维化程度显著增加,miR-148b表达显著上调(P<0.01);miR-148b与预测靶基因PTEN mRNA有结合位点;大鼠心肌梗死组,梗死周边区PTEN表达显著下调(P<0.01);在心脏成纤维细胞中过表达miR-148b,PTEN的蛋白表达水平显著下调(P<0.01),α-SMA蛋白表达水平显著上调(P<0.01),细胞增殖能力显著增强(P<0.05);在AngII诱导心肌纤维化细胞模型中,抑制miR-148b,PTEN蛋白表达水平显著上调(P<0.05),α-SMA蛋白表达水平显著下调(P<0.01),心脏成纤维细胞增殖显著减少(P<0.01)。结论 miR-148b通过PTEN参与心肌梗死后心脏纤维化作用。
Abstract:
AIM To explore the role and mechanisms of miR-148b involved in cardiac fibrosis after myocardial infarction. METHODS The myocardial infarction model was induced by ligation of the left anterior descending coronary artery of rats. The target of miR-148b was predicted using bioinformatic methods. The expression level of miR-148b in rat heart tissue was evaluated using real-time PCR. The expression level of PTEN and α-SMA protein in rat heart tissue was evaluated using Western blot. Cardiac fibroblast proliferative ability was assessed using MTT assay and cardiac fibrosis was analyzed using Sirius red staining. RESULTS After myocardial infarction, fibrosis tissue increased and expression of miR-148b was up-regulated significantly in the border zone (P<0.01). The binding sites between miR-148b and PTEN mRNA were found. After myocardial infarction, the expression of PTEN was significantly down-regulated in the border zone (P<0.01). In the cardiac fibroblasts, miR-148b was overexpressed, PTEN protein expression level was significantly down-regulated (P<0.01), α-SMA protein expression level was significantly up-regulated (P<0.01) and the proliferation of cardiac fibroblasts significantly increased (P<0.05). In the cardiac fibroblasts stimulated by AngII, miR-148b was inhibited, PTEN protein expression level was significantly up-regulated (P<0.05), α-SMA protein expression level was significantly down-regulated (P<0.01) and the proliferation of cardiac fibroblasts was significantly decreased (P<0.01). CONCLUSION miR-148b is involved in cardiac fibrosis via PTEN after myocardial infarction.

参考文献/References

[1]Van den Borne SW,Diez J,Blankesteijn WM,et al.Myocardial remodeling after infarction:the role of myofibroblasts[J].Nat Rev Cardiol,2010,7(1):30-37.
[2]Sutton MG,Sharpe N.Left ventricular remodeling after myocardial infarction:pathophysiology and therapy[J].Circulation,2000,101(25):2981-2988.
[3]Spinale FG.Matrix remodeling and the matrix metalloproteinases:influence on cardiac form and function[J].Physiol Rev, 2007, 87(4):1285-1342.
[4]Baek D,Villen J,Shin C,et al.The impact of microRNAs on protein output[J].Nature,2008,455(7209):64-71.
[5]Selbach M,Schwanhausser B,Thierfelder N,et al.Widespread changes in protein synthesis induced by microRNAs[J].Nature,2008,455(7209):58-63.
[6]Olsen PH,Ambros V.The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation.Dev[J].Biol,1999,216(2):671-680.
[7]van Rooij E,Sutherland LB,Thatcher JE,et al.Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis[J].Proc Natl Acad Sci U S A,2008,105(35):13027-13032.
[8]Pan Z,Sun X,Shan H,et al.miR-101 Inhibited Post-Infarct Cardiac Fibrosis and Improved Left Ventricular Compliance via FOS/TGFbeta1 Pathway[J].Circulation,2012,126(7):840-850.
[9]Sen CK,Roy S.MicroRNA 21 in tissue injury and inflammation[J].Cardiovasc Res,2012,96(2):230-233.
[10]Ramani R,Vela D,Sequra A,et al.A microRNA signature associated with recovery from assist device support in two groups of patients with severe heart failure[J].J Am Coll Cardiol,2011,58(22):2270-2278.
[11]van de vire M,Heymans S,Schroen B.MicroRNA involvement in immune activation during heart failure[J].Cardiovasc Drugs Ther,2011,25(2):161-170.
[12]Cheng K,Malliaras K,Shen D,et al.Intramyocardial injection of platelet gel promotes endogenous repair and augments cardiac function in rats with myocardial infarction[J].J Am Coll Cardiol,2012,59(3):256-264.
[13]Simpson P,Savion S.Differentiation of rat myocytes in single cell cultures with and without proliferating nonmyocardial cells.Cross-striations,ultrastructure, and chronotropic response to isoproterenol[J].Circ Res,1982,50(1):101-116.
[14]Garza MA,Wason EA,Zhang JQ.Cardiac remodeling and physical training post myocardial infarction[J].World J Cardiol,2015,7(2):52-64.
[15]Chitnis NS,pytel D,Bobrovnikova-Marjon E,et al.miR-211 is a prosurvival microRNA that regulates chop expression in a PERK-dependent manner[J].Mol Cell,2012,48(3):353-364.
[16]Byrd AE,Aragon IV,Brewer JW. MicroRNA-30c-2* limits expression of proadaptive factor XBP1 in the unfolded protein response[J].J Cell Biol,2012,196(6):689-698.
[17]McClelland AD,Herman-Edelstein M,Komers R,et al.miR-21 promotes renal fibrosis in diabetic nephropathy by targeting PTEN and SMAD7[J].Clin Sci,2015,129(12):1237-1247.
[18]Liu S,Parapuram SK,Leask A.Fibrosis caused by loss of PTEN expression in mouse fibroblasts is crucially dependent on CCN2[J].Arthritis Rheum,2013,65(11):2940-2944.

备注/Memo

备注/Memo:
收稿日期:2015-11-23.
基金项目:国家自然科学青年基金项目资助(81400181)
通讯作者:刘仲伟,主治医师,主要从事心力衰竭及糖尿病心肌病研究 Email:liuzhongweicn@gmail.com
作者简介:赵娜,主治医师,博士 Email:173307845@qq.com
更新日期/Last Update: 2016-10-11