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: potential mediators and biomarkers of diabetic complications
TL;DR: The role of miRNAs in the pathobiology of various diabetic complications, their involvement in oxidant stress, and also the potential use of differentially expressed mi RNAs as novel diagnostic biomarkers and therapeutic targets are discussed.
Journal ArticleDOI
Cross talk between cardiac myocytes and fibroblasts: from multiscale investigative approaches to mechanisms and functional consequences
TL;DR: Targeting cross talk between CM and CF could potentially be used therapeutically for the modulation of the cardiac remodeling response in the diseased heart and may lead to new strategies for the treatment of heart failure or rhythm disturbances.
Journal ArticleDOI
Non-Coding RNAs Including miRNAs and lncRNAs in Cardiovascular Biology and Disease
Masaharu Kataoka,Da-Zhi Wang +1 more
TL;DR: This work reviews the emerging field of non-coding RNAs, including microRNAs (miRNAs) and long non-C coding RNAs (lncRNAs), and their role in cardiovascular function and disease.
Journal ArticleDOI
HMGB1 Attenuates Cardiac Remodelling in the Failing Heart via Enhanced Cardiac Regeneration and miR-206- Mediated Inhibition of TIMP-3
Federica Limana,Grazia Esposito,Daniela D'Arcangelo,Anna Di Carlo,Sveva Romani,Guido Melillo,Antonella Mangoni,Chiara Bertolami,Giulio Pompilio,Antonia Germani,Maurizio C. Capogrossi +10 more
TL;DR: HMGB1 injected into chronically failing hearts enhanced LV function and attenuated LV remodelling; these effects were associated with cardiac regeneration, increased collagenolytic activity, miR-206 overexpression and miR -mediated inhibition of TIMP-3.
Journal ArticleDOI
MicroRNA-21 prevents excessive inflammation and cardiac dysfunction after myocardial infarction through targeting KBTBD7.
Linshan Yang,Bo Wang,Bo Wang,Qingqing Zhou,Yiru Wang,Xingguang Liu,Zhongmin Liu,Zhenzhen Zhan +7 more
TL;DR: It is demonstrated that miR-21 attenuates inflammation, cardiac dysfunction, and maladaptive remodeling post MI through targeting KBTBD7 and inhibiting p38 and NF-κB signaling activation, suggesting that mi R-21 may function as a novel potential therapeutic target for MI.
References
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