Human Gene Set: THUM_MIR21_TARGETS_HEART_DISEASE_UP

For the Mouse gene set with the same name, see THUM_MIR21_TARGETS_HEART_DISEASE_UP

Standard name THUM_MIR21_TARGETS_HEART_DISEASE_UP
Systematic name M13796
Brief description Genes up-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
      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: upregulated genes
Related gene sets (show 1 additional gene sets from the source publication)

(show 46 gene sets from the same authors)
External links
Filtered by similarity ?
Source species Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
Source platform or
identifier namespace
AFFY_Mouse430
Dataset references  
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? NG-CHM interactive heatmaps
(Please note that clustering takes a few seconds)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)

Legacy heatmaps (PNG)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 18 genes
Gene families ? Categorize these 18 genes by gene family
Show members (show 19 source identifiers mapped to 18 genes)
Version history 3.0: First introduced

See MSigDB license terms here. Please note that certain gene sets have special access terms.