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

Faye M. Drawnel, Dagmar Wachten, Jeffery D. Molkentin, Marjorie Maillet, Jan Magnus Aronsen, Fredrik Swift, Ivar Sjaastad, Ning Liu, Daniele Catalucci, Katsuhiko Mikoshiba, Chihiro Hisatsune, Hanneke Okkenhaug, Simon R. Andrews, Martin D. Bootman, H. Llewelyn Roderick

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)783-798
Number of pages16
JournalJournal of Cell Biology
Volume199
Issue number5
DOIs
Publication statusPublished - Nov 2012

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Cardiomegaly
MicroRNAs
Calcium
Inositol 1,4,5-Trisphosphate Receptors
Calcium Signaling
Calcium Channels
Hypertrophy
Cardiac Arrhythmias
Myocardium
Gene Expression
Pressure
Muscles

ASJC Scopus subject areas

  • Cell Biology

Cite this

Drawnel, F. M., Wachten, D., Molkentin, J. D., Maillet, M., Aronsen, J. M., Swift, F., ... Roderick, H. L. (2012). Mutual antagonism between IP3RII and miRNA-133a regulates calcium signals and cardiac hypertrophy. Journal of Cell Biology, 199(5), 783-798. https://doi.org/10.1083/jcb.201111095

Mutual antagonism between IP3RII and miRNA-133a regulates calcium signals and cardiac hypertrophy. / Drawnel, Faye M.; Wachten, Dagmar; Molkentin, Jeffery D.; Maillet, Marjorie; Aronsen, Jan Magnus; Swift, Fredrik; Sjaastad, Ivar; Liu, Ning; Catalucci, Daniele; Mikoshiba, Katsuhiko; Hisatsune, Chihiro; Okkenhaug, Hanneke; Andrews, Simon R.; Bootman, Martin D.; Roderick, H. Llewelyn.

In: Journal of Cell Biology, Vol. 199, No. 5, 11.2012, p. 783-798.

Research output: Contribution to journalArticle

Drawnel, FM, Wachten, D, Molkentin, JD, Maillet, M, Aronsen, JM, Swift, F, Sjaastad, I, Liu, N, Catalucci, D, Mikoshiba, K, Hisatsune, C, Okkenhaug, H, Andrews, SR, Bootman, MD & Roderick, HL 2012, 'Mutual antagonism between IP3RII and miRNA-133a regulates calcium signals and cardiac hypertrophy', Journal of Cell Biology, vol. 199, no. 5, pp. 783-798. https://doi.org/10.1083/jcb.201111095
Drawnel, Faye M. ; Wachten, Dagmar ; Molkentin, Jeffery D. ; Maillet, Marjorie ; Aronsen, Jan Magnus ; Swift, Fredrik ; Sjaastad, Ivar ; Liu, Ning ; Catalucci, Daniele ; Mikoshiba, Katsuhiko ; Hisatsune, Chihiro ; Okkenhaug, Hanneke ; Andrews, Simon R. ; Bootman, Martin D. ; Roderick, H. Llewelyn. / Mutual antagonism between IP3RII and miRNA-133a regulates calcium signals and cardiac hypertrophy. In: Journal of Cell Biology. 2012 ; Vol. 199, No. 5. pp. 783-798.
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