RGD Reference Report - IRF8 suppresses pathological cardiac remodelling by inhibiting calcineurin signalling. - Rat Genome Database

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IRF8 suppresses pathological cardiac remodelling by inhibiting calcineurin signalling.

Authors: Jiang, DS  Wei, X  Zhang, XF  Liu, Y  Zhang, Y  Chen, K  Gao, L  Zhou, H  Zhu, XH  Liu, PP  Bond Lau, W  Ma, X  Zou, Y  Zhang, XD  Fan, GC  Li, H 
Citation: Jiang DS, etal., Nat Commun. 2014;5:3303. doi: 10.1038/ncomms4303.
RGD ID: 11251869
Pubmed: PMID:24526256   (View Abstract at PubMed)
PMCID: PMC3929801   (View Article at PubMed Central)
DOI: DOI:10.1038/ncomms4303   (Journal Full-text)

Interferon regulatory factor 8 (IRF8) is known to affect the innate immune response, for example, by regulating the differentiation and function of immune cells. However, whether IRF8 can influence cardiac hypertrophy is unknown. Here we show that IRF8 levels are decreased in human dilated/hypertrophic cardiomyopathic hearts and in murine hypertrophic hearts. Mice overexpressing Irf8 specifically in the heart are resistant to aortic banding (AB)-induced cardiac hypertrophy, whereas mice lacking IRF8 either globally or specifically in cardiomyocytes develop an aggravated phenotype induced by pressure overload. Mechanistically, we show that IRF8 directly interacts with NFATc1 to prevent NFATc1 translocation and thus inhibits the hypertrophic response. Inhibition of NFATc1 ameliorates the cardiac abnormalities in IRF8(-/-) mice after AB. In contrast, constitutive activation of NFATc1 nullifies the protective effects of IRF8 on cardiac hypertrophy in IRF8-overexpressing mice. Our results indicate that IRF8 is a potential therapeutic target in pathological cardiac hypertrophy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cardiomyopathy amelioratesISOIrf8 (Mus musculus)11251869; 11251869 RGD 
cardiomyopathy amelioratesIMP 11251869 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Irf8  (interferon regulatory factor 8)

Genes (Mus musculus)
Irf8  (interferon regulatory factor 8)

Genes (Homo sapiens)
IRF8  (interferon regulatory factor 8)


Additional Information