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
Circulating miR-29a, among other up-regulated microRNAs, is the only biomarker for both hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy
Roberta Roncarati,Chiara Viviani Anselmi,Maria Angela Losi,Laura Papa,Elena Cavarretta,Paula A. da Costa Martins,Carla Contaldi,Gloria Saccani Jotti,Anna Franzone,Laura Galastri,Michael V.G. Latronico,Massimo Imbriaco,Giovanni Esposito,Leon J. De Windt,Sandro Betocchi,Gianluigi Condorelli +15 more
TL;DR: The data suggest that cardiac remodeling associated with HCM determines a significant release of miRNAs into the bloodstream: the circulating levels of both cardiac- and non-cardiac-specific miRNas are significantly increased in the plasma of HCM patients.
Journal ArticleDOI
MicroRNA-29c Is a Signature MicroRNA under High Glucose Conditions That Targets Sprouty Homolog 1, and Its in Vivo Knockdown Prevents Progression of Diabetic Nephropathy *
TL;DR: Functionally, it is found that miR-29c induces cell apoptosis and increases extracellular matrix protein accumulation and knockdown by a specific antisense oligonucleotide significantly reduced albuminuria and kidney mesangial matrix accumulation in the db/db mice model in vivo.
Journal ArticleDOI
MicroRNA-24 regulates cardiac fibrosis after myocardial infarction.
Jue Wang,Weicong Huang,Weicong Huang,Ruixia Xu,Yu Nie,Xiaoqing Cao,Jiang Meng,Xiuqin Xu,Shengshou Hu,Zhe Zheng +9 more
TL;DR: The findings suggest that miR‐24 has a critical role in CF function and cardiac fibrosis after MI through a furin–TGF‐β pathway and may be used as a target for treatment of MI and other fibrotic heart diseases.
PatentDOI
Micrornas in idiopathic pulmonary fibrosis
Hanadie Yousef,Naftali Kaminski,Panayiotis V. Benos,David L. Corcoran,Pandit V. Kusum,Jadranka Milosevic +5 more
TL;DR: In this article, the discovery that certain microRNAs are differentially expressed in Idiopathic Pulmonary Fibrosis (IPF) was made and diagnostic methods, therapeutic methods, and kits related to these differentially expressing microRNA were developed.
Journal ArticleDOI
MicroRNA let-7c Regulates Macrophage Polarization
Sami Banerjee,Na Xie,Huachun Cui,Zheng Tan,Shanzhong Yang,Mert Icyuz,Edward Abraham,Gang Liu +7 more
TL;DR: Let-7c regulates bactericidal and phagocytic activities of macrophages, two functional phenotypes implicated in macrophage polarization and targets C/EBP-δ, a transcriptional factor that plays an important role in inflammatory response.
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
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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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Alessandra Carè,Daniele Catalucci,Federica Felicetti,Désirée Bonci,Antonio Addario,Paolo Gallo,Marie Louise Bang,Patrizia Segnalini,Yusu Gu,Nancy D. Dalton,Leonardo Elia,Michael V.G. Latronico,Morten A. Høydal,Camillo Autore,Matteo Antonio Russo,Gerald W. Dorn,Øyvind Ellingsen,Pilar Ruiz-Lozano,Kirk L. Peterson,Carlo M. Croce,Cesare Peschle,Gianluigi Condorelli +21 more