TY - JOUR
T1 - Mutual antagonism between IP3RII and miRNA-133a regulates calcium signals and cardiac hypertrophy
AU - Drawnel, Faye M.
AU - Wachten, Dagmar
AU - Molkentin, Jeffery D.
AU - Maillet, Marjorie
AU - Aronsen, Jan Magnus
AU - Swift, Fredrik
AU - Sjaastad, Ivar
AU - Liu, Ning
AU - Catalucci, Daniele
AU - Mikoshiba, Katsuhiko
AU - Hisatsune, Chihiro
AU - Okkenhaug, Hanneke
AU - Andrews, Simon R.
AU - Bootman, Martin D.
AU - Roderick, H. Llewelyn
PY - 2012/11
Y1 - 2012/11
N2 - 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 ectopiccalcium 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-133adown-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 bothan initiating event and a driving force for pathological remodeling.
AB - 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 ectopiccalcium 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-133adown-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 bothan initiating event and a driving force for pathological remodeling.
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U2 - 10.1083/jcb.201111095
DO - 10.1083/jcb.201111095
M3 - Article
C2 - 23166348
AN - SCOPUS:84872001045
SN - 0021-9525
VL - 199
SP - 783
EP - 798
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 5
ER -