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
microRNA regulation of Wnt signaling pathways in development and disease
TL;DR: A fundamental understanding of miRNA functions in Wnt signaling transduction pathways may yield new insight into crosstalks of regulatory mechanisms essential for development and disease pathophysiology leading to novel therapeutics.
Journal ArticleDOI
MicroRNAs and atrial fibrillation: mechanisms and translational potential
TL;DR: A comprehensive analysis of the current experimental evidence supporting miRNAs as important factors in AF and their therapeutic implications is provided, followed by experimental evidence for miRNA-mediated regulation of AF, and a comprehensive overview of miRN as potential novel therapeutic targets for AF are provided.
Journal ArticleDOI
Identification of Sensitive Serum microRNA Biomarkers for Radiation Biodosimetry
Naduparambil K. Jacob,James V. Cooley,Tamara N. Yee,Jidhin Jacob,Hansjuerg Alder,Priyankara Wickramasinghe,Kirsteen H. Maclean,Arnab Chakravarti +7 more
TL;DR: This study has identified several markers useful for evaluation of an individual’s response by minimally invasive methods, relevant to triage in case of a radiation accident and evaluation of toxicity and response during and after therapeutic radiation.
Journal ArticleDOI
MicroRNA‐101 suppresses liver fibrosis by targeting the TGFβ signalling pathway
Xiaolong Tu,Haiyan Zhang,Jingcheng Zhang,Shuhua Zhao,Xiuxiu Zheng,Zhengping Zhang,Jie Zhu,Jiangning Chen,Lei Dong,Yuhui Zang,Junfeng Zhang +10 more
TL;DR: It is demonstrated that the miR‐101 family members act as suppressors of TGFβ signalling by targeting TβRI and its transcriptional activator Kruppel‐like factor 6 (KLF6) during liver fibrogenesis, suggesting that it could be a potential therapeutic target for liver fibrosis.
Journal ArticleDOI
Sprouty proteins: modified modulators, matchmakers or missing links?
TL;DR: The collective evidence points to Sprouty proteins as being substantially covalently-modified to control its location, stability, association, and destruction.
References
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A microRNA component of the p53 tumour suppressor network
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