微RNA三三和心肌肥厚钙调磷酸酯酶控制的相互抑制(英文)教材.pptVIP

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 Overexpression of calcineurin in mouse causes sudden cardiac death associated with decreased density of K channels Deli Dong. et al. Cardiovascular Research 57 (2003) 320–332 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 Carè 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 Carè A et al. Nat Med. 2007;13(5):613-8. Aug.20-22,2009.Dalian 6. Inhibition of miR-133 induces cardiac hypertrophy Carè 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 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 (50μM). A B C Aug.20-22,2009.Dalian Results: Calcineurin/NFAT Signaling Regulates miR-133 Exp