Journal ArticleDOI
MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts
Thomas Thum,Carina Gross,Jan Fiedler,Thomas Fischer,Stephan Kissler,Markus Bussen,Paolo Galuppo,Steffen Just,Wolfgang Rottbauer,Stefan Frantz,Mirco Castoldi,Jürgen Soutschek,Victor Koteliansky,Andreas Rosenwald,M. Albert Basson,Jonathan D. Licht,John T. R. Pena,Sara H. Rouhanifard,Martina U. Muckenthaler,Thomas Tuschl,Gail R. Martin,Johann Bauersachs,Stefan Engelhardt,Stefan Engelhardt +23 more
TLDR
It is shown that microRNA-21 regulates the ERK–MAP kinase signalling pathway in cardiac fibroblasts, which has impacts on global cardiac structure and function and confirms miR-21 as a disease target in heart failure and establishes the therapeutic efficacy of microRNA therapeutic intervention in a cardiovascular disease setting.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.read more
Citations
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Journal ArticleDOI
Deep Sequencing Analysis of miRNA Expression in Breast Muscle of Fast-Growing and Slow-Growing Broilers
TL;DR: Breast muscle tissues of the two-tail samples from Recessive White Rock and Xinghua Chickens were performed on high throughput small RNA deep sequencing to investigate the function of miRNAs in chicken growth, and growth hormone receptor was confirmed as a target of miR-146b-3p by dual-luciferase assay and qPCR.
Journal ArticleDOI
Circulatory miR-133b and miR-21 as Novel Biomarkers in Early Prediction and Diagnosis of Coronary Artery Disease.
Dinesh Kumar,Rajiv Narang,Vishnubhatla Sreenivas,Vandana Rastogi,Jagriti Bhatia,Daman Saluja,Kamna Srivastava +6 more
TL;DR: Assessment of the level of circulatory microRNAs as candidates of novel biomarkers in patients with CAD suggests that miR-133b and MiR-21 could be possible candidates of novels in early prediction of CAD.
Journal ArticleDOI
Mesenchymal Stem Cell Derived Extracellular Vesicles Ameliorate Kidney Injury in Aristolochic Acid Nephropathy.
Sharad Kholia,Maria Beatriz Herrera Sanchez,Massimo Cedrino,Elli Papadimitriou,Marta Tapparo,Maria Chiara Deregibus,Stefania Bruno,Federica Antico,Maria Felice Brizzi,Peter J. Quesenberry,Giovanni Camussi +10 more
TL;DR: It is suggested that MSC-EVs could play a regenerative and anti-fibrotic role in AAN through the transfer of biologically active cargo that regulates the disease both at a protein and genetic level.
Journal ArticleDOI
MicroRNAs in lipid metabolism and atherosclerosis.
TL;DR: Understanding of the specific roles of miRNAs in the distinct cell types involved in atherosclerosis initiation, progression and resolution may reveal new intervention strategies for the prevention and treatment of atherosclerotic cardiovascular disease.
Journal ArticleDOI
Circulating microribonucleic acids miR-1, miR-21 and miR-208a in patients with symptomatic heart failure: Preliminary results.
Grażyna Sygitowicz,Mariusz Tomaniak,Olga Błaszczyk,Łukasz Kołtowski,Krzysztof J. Filipiak,Dariusz Sitkiewicz +5 more
TL;DR: Dysregulation ofmiR-1 and miR-21 expression may be essential for the development of HF; mi R-1 might become a biomarker for predicting HF exacerbation.
References
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Journal ArticleDOI
MicroRNAs: Genomics, Biogenesis, Mechanism, and Function
TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
Journal ArticleDOI
The functions of animal microRNAs
TL;DR: Evidence is mounting that animal miRNAs are more numerous, and their regulatory impact more pervasive, than was previously suspected.
Journal ArticleDOI
Silencing of microRNAs in vivo with ‘antagomirs’
Jan Krützfeldt,Nikolaus Rajewsky,Ravi Braich,Kallanthottathil G. Rajeev,Thomas Tuschl,Muthiah Manoharan,Markus Stoffel +6 more
TL;DR: It is shown that a novel class of chemically engineered oligonucleotides, termed ‘antagomirs’, are efficient and specific silencers of endogenous miRNA levels in mice and may represent a therapeutic strategy for silencing miRNAs in disease.
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A synthetic inhibitor of the mitogen-activated protein kinase cascade.
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Journal ArticleDOI
A microRNA component of the p53 tumour suppressor network
Lin He,Xingyue He,Xingyue He,Lee P. Lim,Elisa de Stanchina,Elisa de Stanchina,Zhenyu Xuan,Yu Liang,Wen Xue,Lars Zender,Jill F. Magnus,Dana Ridzon,Aimee L. Jackson,Peter S. Linsley,Caifu Chen,Scott W. Lowe,Michele A. Cleary,Gregory J. Hannon +17 more
TL;DR: A family of miRNAs, miR-34a–c, whose expression reflected p53 status is described, whose encoded genes are direct transcriptional targets of p53, whose induction by DNA damage and oncogenic stress depends on p53 both in vitro and in vivo.
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