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
Current Understanding of the Pathophysiology of Myocardial Fibrosis and Its Quantitative Assessment in Heart Failure.
Tong Liu,Deli Song,Jian-Zeng Dong,Pinghui Zhu,Jie Liu,Jie Liu,Wei Liu,Xiaohai Ma,Lei Zhao,Shukuan Ling +9 more
TL;DR: This review summarizes the current knowledge regarding the pathophysiology, quantitative assessment, and novel therapeutic strategies of myocardial fibrosis.
Journal ArticleDOI
The transcardiac gradient of cardio‐microRNAs in the failing heart
TL;DR: The transcardiac gradient of 84 cardio‐microRNAs in healthy and failing hearts is evaluated to determine which microRNAs are released or absorbed by the myocardium in heart failure.
Journal ArticleDOI
Clinical applications of microRNAs
TL;DR: This review summarizes what has been recognized pre-clinically and clinically on diagnostic microRNAs and highlights individual microRNA drugs in running platforms driven by four leading microRNA-therapeutic companies.
Journal ArticleDOI
PAPD5-mediated 3′ adenylation and subsequent degradation of miR-21 is disrupted in proliferative disease
Joost Boele,Helena Persson,Jay W. Shin,Yuri Ishizu,Inga Newie,Rolf Søkilde,Shannon M. Hawkins,Cristian Coarfa,Kazuhiro Ikeda,Ken-ichi Takayama,Kuniko Horie-Inoue,Yoshinari Ando,A. Maxwell Burroughs,Chihiro Sasaki,Chizuru Suzuki,Mizuho Sakai,Shintaro Aoki,Ayumi Ogawa,Akira Hasegawa,Marina Lizio,Kaoru Kaida,Bas Teusink,Piero Carninci,Harukazu Suzuki,Satoshi Inoue,Preethi H. Gunaratne,Carlos Rovira,Yoshihide Hayashizaki,Michiel J. L. de Hoon +28 more
TL;DR: It is found that disruption of the miR-21 adenylation and degradation pathway is a general feature in tumors across a wide range of tissues, as evidenced by data from The Cancer Genome Atlas, as well as in the noncancerous proliferative disease psoriasis.
Journal ArticleDOI
Circulating MicroRNA Signatures of Tumor-Derived Exosomes for Early Diagnosis of Non–Small-Cell Lung Cancer
TL;DR: Reports that plasma and serum DNA microsatellite alterations and methylation in patients with early-resected non–small-cell lung cancer (NSCLC) mirrored identical DNA abnormalities in the tumor provided the first hints that detection of these gene abnormalities in serum or plasma could be useful for both cancer diagnosis and detection of recurrence.
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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