hsa-miR-21

heart failure

Relationship type:

Causal

Detection method for miRNA expression:

northern blot, qRT-PCR etc

up-regulated

Validated targets of miRNA from the reference:

Spry1

Validated targets of miRNA from TarBase:

PTEN,TPM1 : More...

Description:

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.

Reference:

MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. | PMID:19043405
Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M, Galuppo P, Just S,
Nature. 2008 Dec 18;456(7224):980-4. Epub 2008 Nov 30.