Mutual antagonism between IP3RII and miRNA-133a regulates calcium signals and cardiac hypertrophy

被引：87

作者：

Drawnel, Faye M. ^{[1
]}

Wachten, Dagmar ^{[1
,2
]}

Molkentin, Jeffery D. ^{[3
]}

Maillet, Marjorie ^{[3
]}

Aronsen, Jan Magnus ^{[4
,5
]}

Swift, Fredrik ^{[4
]}

Sjaastad, Ivar ^{[4
]}

Liu, Ning ^{[6
]}

Catalucci, Daniele ^{[7
,8
]}

Mikoshiba, Katsuhiko ^{[9
]}

Hisatsune, Chihiro ^{[9
]}

Okkenhaug, Hanneke ^{[1
]}

Andrews, Simon R. ^{[1
]}

Bootman, Martin D. ^{[1
]}

Roderick, H. Llewelyn ^{[1
,10
]}

机构：

[1] Babraham Inst, Cambridge CB22 3AT, England

[2] Ctr Adv European Studies & Res, Dept Mol Sensory Syst, D-53175 Bonn, Germany

[3] Univ Cincinnati, Dept Pediat, Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA

[4] Oslo Univ Hosp, Inst Expt Med Res, Fac Med, N-0407 Oslo, Norway

[5] Bjorknes Coll, N-0456 Oslo, Norway

[6] UT SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA

[7] Humanitas Clin & Res Ctr, I-20089 Milan, Italy

[8] CNR, Inst Genet & Biomed Res, Milan Sect, I-20138 Milan, Italy

[9] RIKEN Brain Sci Inst, Lab Dev Neurobiol, Wako, Saitama 5310198, Japan

[10] Univ Cambridge, Dept Pharmacol, Cambridge CB2 1PD, England

来源：

JOURNAL OF CELL BIOLOGY | 2012年 / 199卷 / 05期

基金：

英国生物技术与生命科学研究理事会;

关键词：

SERUM RESPONSE FACTOR; MUSCLE GENE-EXPRESSION; CA2+ RELEASE; MICRORNAS; HEART; MYOCYTES; TARGETS; REPRESSION; RECEPTORS; IDENTIFICATION;

D O I：

10.1083/jcb.201111095

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Inositol 1,4,5'-triphosphate receptor II (IP3RII) calcium channel expression is increased in both hypertrophic failing human myocardium and experimentally induced models of the disease. The ectopic calcium released from these receptors induces pro-hypertrophic gene expression and may promote arrhythmias. Here, we show that IP3RII expression was constitutively restrained by the muscle-specific miRNA, miR-133a. During the hypertrophic response to pressure overload or neurohormonal stimuli, miR-133a down-regulation permitted IP3RII levels to increase, instigating pro-hypertrophic calcium signaling and concomitant pathological remodeling. Using a combination of in vivo and in vitro approaches, we demonstrated that IP3-induced calcium release (IICR) initiated the hypertrophy-associated decrease in miR-133a. In this manner, hypertrophic stimuli that engage IICR set a feedforward mechanism in motion whereby IICR decreased miR-133a expression, further augmenting IP3RII levels and therefore pro-hypertrophic calcium release. Consequently, IICR can be considered as both an initiating event and a driving force for pathological remodeling.

引用

页码：783 / 798

页数：16

共 54 条

[1]

Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs [J].