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
Downregulation of miR-192 causes hepatic steatosis and lipid accumulation by inducing SREBF1: Novel mechanism for bisphenol A-triggered non-alcoholic fatty liver disease.
Yi Lin,Dongxiao Ding,Qiansheng Huang,Qiong Liu,Haoyang Lu,Yanyang Lu,Yulang Chi,Xia Sun,Guozhu Ye,Huimin Zhu,Jie Wei,Sijun Dong +11 more
TL;DR: In this article, BPA-induced hepatic steatosis and lipid accumulation were associated with decreased expression of miR-192, upregulation of SREBF1 and a series of genes involved in de novo lipogenesis.
Journal ArticleDOI
Blood-based microRNA signatures differentiate various forms of cardiac hypertrophy.
Anselm A. Derda,Sabrina Thum,Johan M. Lorenzen,Udo Bavendiek,Joerg Heineke,Britta Keyser,Manfred Stuhrmann,Raymond C. Givens,Peter J. Kennel,P. Christian Schulze,Julian D. Widder,Johann Bauersachs,Thomas Thum,Thomas Thum +13 more
TL;DR: It is demonstrated that miR-29a and miC-29c show a specific signature to distinguish between aortic stenosis, hypertrophic non-obstructive and obstructive cardiomyopathies and thus could be developed into clinically useful biomarkers.
Journal ArticleDOI
Heart Failure With Preserved Ejection Fraction: A Review of Cardiac and Noncardiac Pathophysiology.
TL;DR: The potential of exercise training is addressed, which is currently the only available therapy to improve aerobic capacity and quality of life inHFpEF patients, and the underlying mechanisms responsible for this improvement could lead to new biomarkers and therapeutic targets for HFpEF.
Journal ArticleDOI
Circulating cardiovascular microRNAs in critically ill COVID-19 patients.
Ankita Garg,Benjamin Seeliger,Anselm A. Derda,Ke Xiao,Anika Gietz,Kristian Scherf,Kristina Sonnenschein,Isabell Pink,Marius M. Hoeper,Tobias Welte,Johann Bauersachs,Sascha David,Sascha David,Christian Bär,Thomas Thum,Thomas Thum +15 more
TL;DR: In this paper, the miR profiles were able to differentiate between severely ill, mechanically-ventilated influenza-associated acute respiratory distress syndrome (Influenza-ARDS) and COVID-19 patients, indicating a rather specific response and cardiac involvement.
Journal ArticleDOI
The Anti-fibrotic Effects and Mechanisms of MicroRNA-486-5p in Pulmonary Fibrosis
Xiaoming Ji,Baiqun Wu,Jingjing Fan,Ruhui Han,Chen Luo,Ting Wang,Jingjin Yang,Lei Han,Lei Han,Baoli Zhu,Dong Wei,Jingyu Chen,Chunhui Ni +12 more
TL;DR: Results indicate that miR-486-5p may inhibit fibrosis, as determined by luciferase assays and Western blotting and to test the potential therapeutic significance of this miRNA, it is shown that it is overexpressed in animal models.
References
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Journal ArticleDOI
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A microRNA component of the p53 tumour suppressor network
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