RGD Reference Report - MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. - Rat Genome Database

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MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts.

Authors: Thum, Thomas  Gross, Carina  Fiedler, Jan  Fischer, Thomas  Kissler, Stephan  Bussen, Markus  Galuppo, Paolo  Just, Steffen  Rottbauer, Wolfgang  Frantz, Stefan  Castoldi, Mirco  Soutschek, Jürgen  Koteliansky, Victor  Rosenwald, Andreas  Basson, M Albert  Licht, Jonathan D  Pena, John T R  Rouhanifard, Sara H  Muckenthaler, Martina U  Tuschl, Thomas  Martin, Gail R  Bauersachs, Johann  Engelhardt, Stefan 
Citation: Thum T, etal., Nature. 2008 Dec 18;456(7224):980-4. doi: 10.1038/nature07511. Epub 2008 Nov 30.
RGD ID: 41404712
Pubmed: PMID:19043405   (View Abstract at PubMed)
DOI: DOI:10.1038/nature07511   (Journal Full-text)

MicroRNAs comprise a broad class of small non-coding RNAs that control expression of complementary target messenger RNAs. Dysregulation of microRNAs by several mechanisms has been described in various disease states including cardiac disease. Whereas previous studies of cardiac disease have focused on microRNAs that are primarily expressed in cardiomyocytes, the role of microRNAs expressed in other cell types of the heart is unclear. Here we show that microRNA-21 (miR-21, also known as Mirn21) regulates the ERK-MAP kinase signalling pathway in cardiac fibroblasts, which has impacts on global cardiac structure and function. miR-21 levels are increased selectively in fibroblasts of the failing heart, augmenting ERK-MAP kinase activity through inhibition of sprouty homologue 1 (Spry1). This mechanism regulates fibroblast survival and growth factor secretion, apparently controlling the extent of interstitial fibrosis and cardiac hypertrophy. In vivo silencing of miR-21 by a specific antagomir in a mouse pressure-overload-induced disease model reduces cardiac ERK-MAP kinase activity, inhibits interstitial fibrosis and attenuates cardiac dysfunction. These findings reveal that microRNAs can contribute to myocardial disease by an effect in cardiac fibroblasts. Our results validate miR-21 as a disease target in heart failure and establish the therapeutic efficacy of microRNA therapeutic intervention in a cardiovascular disease setting.



Disease Annotations    
congestive heart failure  (IEP,IMP,ISO)

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Mir21  (microRNA 21)

Genes (Mus musculus)
Mir21a  (microRNA 21a)

Genes (Homo sapiens)
MIR21  (microRNA 21)


Additional Information