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
MicroRNAs in diabetes: tiny players in big disease.
TL;DR: This review focuses on and discusses the current diabetic epidemic and the potential role(s) of these miRNAs in various physiological processes that lead to the diabetic phenotype with an objective of better understanding the emerging mechanisms of these small molecules in the development and progression of diabetes and its complications.
Journal ArticleDOI
MicroRNA in Cancer: The Involvement of Aberrant MicroRNA Biogenesis Regulatory Pathways
TL;DR: The mechanisms that govern the regulation of miRNA biogenesis are discussed with particular focus on how these mechanisms are perturbed in cancer.
Journal ArticleDOI
Extracellular Matrix Secretion by Cardiac Fibroblasts: Role of microRNA-29b and microRNA-30c
Mélanie Abonnenc,Adam Nabeebaccus,Ursula Mayr,Javier Barallobre-Barreiro,Xuebin Dong,Friederike Cuello,Sumon Sur,Ignat Drozdov,Sarah R. Langley,Ruifang Lu,Konstantina Stathopoulou,Athanasios Didangelos,Xiaoke Yin,Wolfram-Hubertus Zimmermann,Ajay M. Shah,Anna Zampetaki,Manuel Mayr +16 more
TL;DR: Proteomic analysis revealed novel molecular targets of miRNAs that are linked to a fibrogenic cardiac phenotype in a mouse model of pathological but not physiological hypertrophy.
Journal ArticleDOI
Biogenesis and Regulation of Cardiovascular MicroRNAs
Johann Bauersachs,Thomas Thum +1 more
TL;DR: Current knowledge about regulation of cardiovascular miRNAs at the transcriptional level by transcription factors, during processing by the Drosha and Dicer complexes and the importance of miRNA modification, editing, and decay mechanisms are summarized.
Journal ArticleDOI
A Resource for the Conditional Ablation of microRNAs in the Mouse
Chong Yon Park,Lukas T. Jeker,Karen Carver-Moore,Alyssia Oh,Huey Jiin Liu,Rachel Cameron,Hunter Richards,Zhongmei Li,David Adler,Yuko Yoshinaga,María Santos Martínez,Michael Nefadov,Abul K. Abbas,Arthur Weiss,Lewis L. Lanier,Pieter J. de Jong,Jeffrey A. Bluestone,Deepak Srivastava,Michael T. McManus,Michael T. McManus +19 more
TL;DR: To unravel in vivo functions of miRNAs, conditional, reporter-tagged knockout-first mice are generated for numerous evolutionarily conserved mi RNAs and in vivo lacZ reporter analysis revealed highly tissue-specific expression patterns and their miRNA expression profiling matched closely with published expression data.
References
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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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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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