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
Atherosclerotic Conditions Promote the Packaging of Functional MicroRNA-92a-3p Into Endothelial Microvesicles
Yangyang Liu,Qian Li,Qian Li,Mohammed Rabiul Hosen,Andreas Zietzer,Anna Flender,Paula Levermann,Theresa Schmitz,Daniel Jw Frühwald,Philip Roger Goody,Georg Nickenig,Nikos Werner,Felix Jansen +12 more
TL;DR: Athrosclerotic conditions promote the packaging of endothelial miR-92a-3p into EMVs, which accelerated cell migration and proliferation in recipient ECs, which accelerate cell migration, proliferation, and blocked vascular network formation in a matrigel plug.
Journal ArticleDOI
PAI-1-regulated miR-21 defines a novel age-associated fibrogenic pathway in muscular dystrophy
Esther Ardite,Eusebio Perdiguero,Berta Vidal,Susana Gutarra,Antonio L. Serrano,Pura Muñoz-Cánoves,Pura Muñoz-Cánoves +6 more
TL;DR: Extracellular proteolysis mediated by the uPA/PAI-1 system determines miR-21 expression in fibroblasts, which affects age-associated fibrogenesis and muscle deterioration in a muscular dystrophy model.
Journal ArticleDOI
MiR-21-5p and miR-126a-3p levels in plasma and circulating angiogenic cells: relationship with type 2 diabetes complications.
Fabiola Olivieri,Liana Spazzafumo,Massimiliano Bonafè,Rina Recchioni,Francesco Prattichizzo,Fiorella Marcheselli,Luigina Micolucci,Emanuela Mensà,Angelica Giuliani,Gabriele Santini,Mirko Gobbi,Raffaella Lazzarini,Massimo Boemi,Roberto Testa,Roberto Antonicelli,Antonio Domenico Procopio,Anna Rita Bonfigli +16 more
TL;DR: Their expression levels in CACs from T2DM with MACE suggest a shift from a proangiogenic to a proinflammatory profile, and Circulating miR-21-5p andmiR-126-3p emerge as dynamic biomarkers of systemic inflammatory/angIogenic status.
Journal ArticleDOI
Myocardial infarction-induced microRNA-enriched exosomes contribute to cardiac Nrf2 dysregulation in chronic heart failure
TL;DR: The regulation of myocardial Nrf2 in the postmyocardial infarction (post-MI) state is investigated, providing a novel mechanism mediated by microRNA-enriched exosomes, contributing to the nuclear factor erythroid 2-related factor 2 dysregulation and subsequent oxidative stress.
Journal ArticleDOI
Targeting microRNAs involved in human diseases: A novel approach for modification of gene expression and drug development
Roberto Gambari,Enrica Fabbri,Monica Borgatti,Ilaria Lampronti,Alessia Finotti,Eleonora Brognara,Nicoletta Bianchi,Alex Manicardi,Rosangela Marchelli,Roberto Corradini +9 more
TL;DR: RNA and DNA analogs, which can selectively target microRNAs using Watson-Crick base pairing schemes, provide a rational and efficient way to modulate gene expression, and peptide nucleic acids, promising tools for the inhibition of miRNA activity, with important applications in gene therapy and in drug development are developed.
References
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Journal ArticleDOI
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Journal ArticleDOI
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Jan Krützfeldt,Nikolaus Rajewsky,Ravi Braich,Kallanthottathil G. Rajeev,Thomas Tuschl,Muthiah Manoharan,Markus Stoffel +6 more
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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
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