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 promotes fibrosis in an acute cardiac allograft transplantation model
Shashi Kumar Gupta,Ryo Itagaki,Xiang Zheng,Sandor Batkai,Sabrina Thum,Fareed Ahmad,Lucas Van Aelst,Amit Sharma,Maria-Teresa Piccoli,Florian Weinberger,Jan Fiedler,Michael Heuser,Stephane Heymans,Christine S. Falk,Reinhold Förster,Sonja Schrepfer,Thomas Thum,Thomas Thum +17 more
TL;DR: In vivo inhibition of miR-21 is a novel strategy to target fibrosis development in cardiac allografts and patients with cardiac rejection after heart transplantation showed increased cardiac miR -21 levels.
Journal ArticleDOI
MicroRNA-21 Aggravates Cyst Growth in a Model of Polycystic Kidney Disease
Ronak Lakhia,Sachin Hajarnis,Darren Williams,Karam Aboudehen,Matanel Yheskel,Chao Xing,Mark E. Hatley,Vicente E. Torres,Darren P. Wallace,Vishal Patel +9 more
TL;DR: RNA sequencing analysis and additional in vivo assays showed that miR-21 inhibits apoptosis of cyst epithelial cells, likely through direct repression of its target gene programmed cell death, and suggest that inhibiting mi R-21 is a potential new therapeutic approach to slow cyst growth in PKD.
Journal ArticleDOI
Characterization of an extensive rainbow trout miRNA transcriptome by next generation sequencing.
Amélie Juanchich,Philippe Bardou,Olivier Rué,Jean-Charles Gabillard,Christine Gaspin,Julien Bobe,Yann Guiguen +6 more
TL;DR: This study represents the first characterization of rainbow trout miRNA transcriptome from a wide variety of tissue and sets an extensive repertoire of rainbow Trout miRNAs, which provide a novel resource to advance genomic research in salmonid species.
Journal ArticleDOI
MicroRNAs in cardiac apoptosis.
TL;DR: The role of miRNAs in regulating cardiac apoptosis is summarized and the potential therapeutic approaches for apoptosis-related cardiac diseases by modulating mi RNAs are discussed.
Journal ArticleDOI
Comparative study of microRNA profiling in keloid fibroblast and annotation of differential expressed microRNAs
TL;DR: It is demonstrated that the miRNA expression profile is altered in KFs compared with in fetal and adult dermal fibroblasts, and the expression profile may provide a useful clue for exploring the pathogenesis of keloids.
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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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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