微RNA-133和心肌肥厚钙调磷酸酯酶控制的相互抑制(英文).ppt
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1、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,Calcineu
2、rin/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 Cardi
3、ac 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.,Au
4、g.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;
5、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 hypertroph
6、y,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 a
7、nd 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 o
8、f 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 sp
9、ecies. *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 l
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- RNA 133 心肌 肥厚 磷酸酯 控制 相互 抑制 英文
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