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-21 in Pancreatic Ductal Adenocarcinoma Tumor-Associated Fibroblasts Promotes Metastasis
Brian E. Kadera,Luyi Li,Paul A. Toste,Nanping Wu,Curtis Adams,David W. Dawson,Timothy R. Donahue +6 more
TL;DR: It is shown that miR-21 expression in PDAC TAFs is associated with decreased overall survival and promotes TC invasion, and anti-miR- 21 may represent a novel therapeutic strategy for dual targeting of both tumor and stroma inPDAC.
Journal ArticleDOI
MicroRNAs are dynamically regulated in hypertrophic hearts, and miR‐199a is essential for the maintenance of cell size in cardiomyocytes
Xiao-Wei Song,Qing Li,Li Lin,Xiao-Chen Wang,Dong-Feng Li,Guokun Wang,An-Jing Ren,Yan-Rong Wang,Yong-wen Qin,Wen-Jun Yuan,Qing Jing +10 more
TL;DR: It is shown that several miRNAs were dynamically regulated in the rat hypertrophic hearts and miR‐199a was up‐regulated by 10‐fold in hypertrophic Hearts after abdominal aorta constriction for 12 weeks and might play a role in the regulation of cardiac hypertrophy.
Journal ArticleDOI
MicroRNA-21 Regulates Vascular Smooth Muscle Cell Function via Targeting Tropomyosin 1 in Arteriosclerosis Obliterans of Lower Extremities
Mian Wang,Wen Li,Guangqi Chang,Cai-Sheng Ye,Jing-Song Ou,Xiao-xi Li,Yong Liu,Tuck-Yun Cheang,Xue-Ling Huang,Shenming Wang +9 more
TL;DR: The results suggest that miR-21 is able to regulate ASMC function by targeting tropomyosin 1, and the hypoxia inducible factor-1 &agr;/miR- 21/tropomyOSin 1 pathway may play a critical role in the pathogenesis of ASO.
Journal ArticleDOI
Plasminogen Activator Inhibitor Type-1 as a Regulator of Fibrosis.
Reyhaneh Rabieian,Maryam Boshtam,Mahshid Zareei,Shirin Kouhpayeh,Aria Masoudifar,Hamed Mirzaei +5 more
TL;DR: This review summarizes the current knowledge of critical pathways that regulate PAI‐1 gene expression and suggests effective approaches for the treatment of fibrotic disease.
Journal ArticleDOI
Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients
Ana V. Villar,Raquel García,David Merino,Miguel Llano,Manuel Cobo,Cecilia Montalvo,Rafael Martín-Durán,María A. Hurlé,J. Francisco Nistal +8 more
TL;DR: The results support the role of miR-21 as a regulator of the fibrotic process that occurs in response to pressure overload in aortic stenosis patients and underscore the value of circulating miR20 as a biomarker for pathological myocardial fibrosis.
References
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