Gene Set: THUM_MIR21_TARGETS_HEART_DISEASE_DN

Standard name THUM_MIR21_TARGETS_HEART_DISEASE_DN
Systematic name M18073
Brief description Genes down-regulated in a mouse model of heart disease whose expression reverted to normal by silencing of MIR21 [GeneID=406991] microRNA.
Full description or abstract 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.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 19043405   Authors: Thum T,Gross C,Fiedler J,Fischer T,Kissler S,Bussen M,Galuppo P,Just S,Rottbauer W,Frantz S,Castoldi M,Soutschek J,Koteliansky V,Rosenwald A,Basson MA,Licht JD,Pena JT,Rouhanifard SH,Muckenthaler MU,Tuschl T,Martin GR,Bauersachs J,Engelhardt S
Exact source Table 2S: downregulated genes
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Organism Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
Source platform AFFY_Mouse430
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