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
miR-21: A Star Player in Cardiac Hypertrophy
TL;DR: Modulation of miRNA levels in vivo reveals their causative role in cardiac remodelling and shows that the therapeutic impact miRNA-based interventions can have in the treatment of various cardiac pathologies.
Journal ArticleDOI
Triggering Endogenous Cardiac Repair and Regeneration via Extracellular Vesicle-Mediated Communication
TL;DR: The role of EV in both regulating cardiac homeostasis and driving heart regeneration and their role in providing cardio-protection and enhancing cardiac repair mechanisms are addressed.
Journal ArticleDOI
Sp1 Mediates a Therapeutic Role of MiR-7a/b in Angiotensin II-Induced Cardiac Fibrosis via Mechanism Involving the TGF-β and MAPKs Pathways in Cardiac Fibroblasts.
Rui Li,Jie Xiao,Xiaoteng Qing,Jun-hui Xing,Yanfei Xia,Jia Qi,Xiaojun Liu,Sen Zhang,Xi Sheng,Xinyu Zhang,Xiaoping Ji +10 more
TL;DR: In this article, the anti-fibrotic mechanism of miR-7a/b in angiotensin II (ANG II)-stimulated cardiac fibroblasts (CFs) was investigated.
Journal ArticleDOI
Regulation of Cardiac Cell Fate by microRNAs: Implications for Heart Regeneration
TL;DR: The role of microRNAs in the control of stem cell and cardiomyocyte dependent cardiac regeneration processes are reviewed, and potential applications for the treatment of cardiac injury are discussed.
Journal Article
Tumor-targeted RNA-interference: functional non-viral nanovectors
TL;DR: The currently recognized RNAi delivery barriers and the anti-barrier requirements related to vectors' properties are summarized and the outstanding needs in the areas of material synthesis and assembly, multifunction combinations, proper delivery and assisting approaches that require more intensive investigation are reviewed.
References
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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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