已阅读5页,还剩21页未读, 继续免费阅读
版权说明:本文档由用户提供并上传,收益归属内容提供方,若内容存在侵权,请进行举报或认领
文档简介
Reciprocal Repression between MicroRNA-133 and Calcineurin Controls Cardiac Hypertrophy: A Novel Mechanism for Progressive Cardiac Hypertrophy,De-Li Dong, Yan-Jie Lu, Bao-Feng Yang (董德利 吕延杰 杨宝峰) Department of Pharmacology Harbin Medical University, P.R.China,Aug.20-22,2009.Dalian,Background,Calcineurin/NFAT pathway induces Cardiac Hypertrophy Calcineurin activation in cardiac hypertrophy Decreased miR-133 expression in cardiac hypertrophy Overexpression of miR-133 inhibits cardiac hypertrophy Inhibition of miR-133 induces cardiac hypertrophy,Aug.20-22,2009.Dalian,1. Calcineurin-Dependent Cardiac Hypertrophy,Jeffery D. Molkentin et al. Cell,1998; 93,215228.,Aug.20-22,2009.Dalian,1. Calcineurin-Dependent Cardiac Hypertrophy,Jeffery D. Molkentin et al. Cell,1998; 93,215228.,Aug.20-22,2009.Dalian,1.Calcineurin-Dependent Cardiac Hypertrophy,Jeffery D. Molkentin et al. Cell,1998; 93,215228.,Aug.20-22,2009.Dalian,Overexpression of calcineurin in mouse causes sudden cardiac death associated with decreased density of K channels,Deli Dong. et al. Cardiovascular Research 57 (2003) 320332,Aug.20-22,2009.Dalian,2. Calcineurin Activation in cardiac hypertrophy,Hae W. Lim et al.Circulation. 2000;101:2431-2437.,Aug.20-22,2009.Dalian,3. Calcineurin/NFAT Coupling Participates in Pathological, but not Physiological, Cardiac Hypertrophy,Wilkins BJ, et al. Circ Res. 2004;94:110-118.,Aug.20-22,2009.Dalian,Car A et al. Nat Med. 2007;13(5):613-8.,4. Decreased miR-133 expression in cardiac hypertrophy,Aug.20-22,2009.Dalian,5. Overexpression of miR-133 inhibits cardiac hypertrophy,Car A et al. Nat Med. 2007;13(5):613-8.,Aug.20-22,2009.Dalian,6. Inhibition of miR-133 induces cardiac hypertrophy,Car A et al. Nat Med. 2007;13(5):613-8.,Aug.20-22,2009.Dalian,Hypothesis: Interaction between miR-133 and calcineurin in cardiac hypertrophy?, Calcineurin is the target of miR-133; The expression of miR-133 is regulated by calcineurin/NFAT signaling pathway.,Calcineurin,miR-133,Cardiac hypertrophy,Aug.20-22,2009.Dalian,Results 1. miR-133 Targets Calcineurin,Figure 1. Post-transcriptional Repression of Calcineurin by miR-133. (A) The sequences showing the unique sites of miRNA:mRNA complementary between miR-133 and calcineurin for rat and mouse genes. (B) Co-transfection of miR-133 with the luciferase reporter gene linked to the 3UTR of calcineurin reduced luciferase activity in rat and mouse species. *P0.01 vs Control; # P0.05 vs miR-133.,0,0.5,1.0,Relative luciferase activity,0,0.5,1.0,NC,miR-133,+AMO-133,miR-133,AMO-133,Mut-133,*,#,#,*,B,Mouse (n=8),Rat (n=10),A,Aug.20-22,2009.Dalian,Results: miR-133 Targets Calcineurin,Fig.2. (A) transfection of miR-133 specifically increased miR-133 level in cultured cardiomyocytes. *P0.01 vs non-transfection group. (B) The negative control (NC) had no effect on miR-133 level, but AMO-133 decreased miR-133 level. *P0.01 vs control (lipofectamine transfection agents). n=3.,A,B,Aug.20-22,2009.Dalian,Results: miR-133 Targets Calcineurin,Fig.3. Effects of miR-133 on calcineurin protein levels (n=5), mRNA level (n=5) and cell area (The number was in brackets) in normal cultured cardiomyoctes. *P0.01 vs Control.,Aug.20-22,2009.Dalian,A,B,C,1. miR-133 Targets Calcineurin,Figure 4. Effects of miR-133 on calcineurin protein levels (n=5), mRNA level (n=5) and cell area (The number of cells was in brackets) in cardiomyoctes treated with PE (50M).,A,B,C,Aug.20-22,2009.Dalian,Results: Calcineurin/NFAT Signaling Regulates miR-133 Expression,Fig.5. Calcineurin inhibitor CsA inhibited cardiac hypertrophy induced by transverse aortic constriction in mice.,Sham,TAC,TAC+CsA,Aug.20-22,2009.Dalian,A,B,Results: Calcineurin/NFAT Signaling Regulates miR-133 Expression,Fig.6. Calcineurin inhibitor CsA inhibited cardiac hypertrophy (The number was in brackets), calcineurin expression (n=5) and activity (n=5). *P0.01 vs Control; #P0.01 vs TAC.,Aug.20-22,2009.Dalian,A,B,C,Results: Calcineurin/NFAT Signaling Regulates miR-133 Expression,Fig.7. CsA restored the decreased miR-133 expression but not the increased miR-195 expression in TAC-induced hypertrophic heart. *P0.01 vs Control. # P0.01 vs TAC; n=5.,Aug.20-22,2009.Dalian,A,B,Results: Calcineurin/NFAT Signaling Regulates miR-133 Expression,Fig.8. Primary rats cardiomyocytes in serum-free medium were stimulated with PE and PE+CsA. Cardiomyocytes were identified with a-actinin antibody (red signal) and nuclei were stained with bis-benzamide (blue).,Control,PE,PE+CsA,Aug.20-22,2009.Dalian,A,B,Results: Calcineurin/NFAT Signaling Regulates miR-133 Expression,Fig.9. CsA inhibited hypertrophy (The number was in brackets), calcineurin expression (n=5) and activity (n=5) in cardiomyocytes treated with PE (50M). *P0.01 vs Control. # P0.01 vs PE.,Aug.20-22,2009.Dalian,A,B,C,Results: Calcineurin/NFAT Signaling Regulates miR-133 Expression,Fig.10. CsA alleviated the decreased miR-133 expression in PE-treated cardiomyocyes. *P0.01 vs Control. #P0.05 vs PE; n=5.,Aug.20-22,2009.Dalian,Results: Calcineurin/NFAT Signaling Regulates miR-133 Expression,Fig.11. Calcineurin/NFAT-dependent Regulation of miR-133. (A) Antisense-A ODNs increased the expression of miR-133 in cultured cardiomyocytes. *P0.01 vs Control; n=4. (B) NFAT decoy ODNs increased the expression
温馨提示
- 1. 本站所有资源如无特殊说明,都需要本地电脑安装OFFICE2007和PDF阅读器。图纸软件为CAD,CAXA,PROE,UG,SolidWorks等.压缩文件请下载最新的WinRAR软件解压。
- 2. 本站的文档不包含任何第三方提供的附件图纸等,如果需要附件,请联系上传者。文件的所有权益归上传用户所有。
- 3. 本站RAR压缩包中若带图纸,网页内容里面会有图纸预览,若没有图纸预览就没有图纸。
- 4. 未经权益所有人同意不得将文件中的内容挪作商业或盈利用途。
- 5. 人人文库网仅提供信息存储空间,仅对用户上传内容的表现方式做保护处理,对用户上传分享的文档内容本身不做任何修改或编辑,并不能对任何下载内容负责。
- 6. 下载文件中如有侵权或不适当内容,请与我们联系,我们立即纠正。
- 7. 本站不保证下载资源的准确性、安全性和完整性, 同时也不承担用户因使用这些下载资源对自己和他人造成任何形式的伤害或损失。
最新文档
- 【正版授权】 IEC 60749-20-1:2009 EN-FR Semiconductor devices - Mechanical and climatic test methods - Part 20-1: Handling,packing,labelling and shipping of surface-mount devices sensitive to the
- 【正版授权】 IEC 60730-2-5:2013/AMD1:2017 EN-FR Amendment 1 - Automatic electrical controls - Part 2-5: Particular requirements for automatic electrical burner control systems
- 【正版授权】 IEC 60730-2-19:1997+AMD1:2000+AMD2:2007 CSV EN-FR Automatic electrical controls for household and similar use - Part 2-19: Particular requirements for electrically operated oil valves
- 【正版授权】 IEC 60695-2-13:2010 EN-FR Fire hazard testing - Part 2-13: Glowing/hot-wire based test methods - Glow-wire ignition temperature (GWIT) test method for materials
- 【正版授权】 IEC 60684-3-247:2019 RLV EN Flexible insulating sleeving - Part 3: Specifications for individual types of sleeving - Sheet 247: Heat-shrinkable,polyolefin sleeving,dual wall,not fl
- 【正版授权】 IEC 60670-1:2002/AMD1:2011 EN-FR Amendment 1 - Boxes and enclosures for electrical accessories for household and similar fixed electrical installations - Part 1: General requirements
- 【正版授权】 IEC 60603-7-51:2010 EN-FR Connectors for electronic equipment - Part 7-51: Detail specification for 8-way,shielded,free and fixed connectors,for data transmissions with frequencies
- 【正版授权】 IEC 60601-2-41:2009+AMD1:2013 CSV EN-FR Medical electrical equipment - Part 2-41: Particular requirementsfor the basic safety and essential performance of surgical luminaires an
- 【正版授权】 IEC 60601-2-2:2017 RLV EN Medical electrical equipment - Part 2-2: Particular requirements for the basic safety and essential performance of high frequency surgical equipment and high
- 【正版授权】 IEC 60601-1:2005/AMD1:2012 EN-FR Amendment 1 - Medical electrical equipment - Part 1: General requirements for basic safety and essential performance
- 2022年广东省初中生物、地理会考真题含答案
- 嘉兴市海宁市长安镇招聘考试真题2022
- 2023年【低压电工、高压电工】考试题库及低压电工新版模拟试题(100题,含答案)
- 线路防护工程施工方案
- 新高考全国Ⅱ卷高考英语试题及答案 真题及答案
- 通信工程投标专家继续教育题库(附答案)
- 2022-2023学年广东省广州市越秀区七年级下学期英语期末模拟试题二(含答案)
- 韩国语topik单词-初级+中级
- 2014xxxxx医学伦理委员会审批件模板
- case-study-模版的主要内容
- 工伤职工旧伤复发治疗申请表
评论
0/150
提交评论