Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis
Eva van Rooij,Lillian B. Sutherland,Jeffrey E. Thatcher,J. Michael DiMaio,R. Haris Naseem,William S. Marshall,Joseph A. Hill,Eric N. Olson +7 more
TLDR
It is concluded that miR-29 acts as a regulator of cardiac fibrosis and represents a potential therapeutic target for tissue fibrosis in general.Abstract:
Acute myocardial infarction (MI) due to coronary artery occlusion is accompanied by a pathological remodeling response that includes hypertrophic cardiac growth and fibrosis, which impair cardiac contractility. Previously, we showed that cardiac hypertrophy and heart failure are accompanied by characteristic changes in the expression of a collection of specific microRNAs (miRNAs), which act as negative regulators of gene expression. Here, we show that MI in mice and humans also results in the dysregulation of specific miRNAs, which are similar to but distinct from those involved in hypertrophy and heart failure. Among the MI-regulated miRNAs are members of the miR-29 family, which are down-regulated in the region of the heart adjacent to the infarct. The miR-29 family targets a cadre of mRNAs that encode proteins involved in fibrosis, including multiple collagens, fibrillins, and elastin. Thus, down-regulation of miR-29 would be predicted to derepress the expression of these mRNAs and enhance the fibrotic response. Indeed, down-regulation of miR-29 with anti-miRs in vitro and in vivo induces the expression of collagens, whereas over-expression of miR-29 in fibroblasts reduces collagen expression. We conclude that miR-29 acts as a regulator of cardiac fibrosis and represents a potential therapeutic target for tissue fibrosis in general.read more
Citations
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Mechanisms of fibrosis: therapeutic translation for fibrotic disease
TL;DR: How cell-intrinsic changes in important structural cells can perpetuate the fibrotic response by regulating the differentiation, recruitment, proliferation and activation of extracellular matrix–producing myofibroblasts is described.
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MicroRNAs in Stress Signaling and Human Disease
Joshua T. Mendell,Eric N. Olson +1 more
TL;DR: Emerging principles of miRNA regulation of stress signaling pathways are reviewed and applied to the authors' understanding of the roles of miRNAs in disease.
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Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches
TL;DR: This review guides the reader through important aspects of non-coding RNA biology, including their biogenesis, mode of actions, physiological function, as well as their role in the disease context (such as in cancer or the cardiovascular system).
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Transcriptional Regulation and Its Misregulation in Disease
Tong Ihn Lee,Richard A. Young +1 more
TL;DR: Recent advances in understanding of transcriptional regulation are reviewed and how these have provided new insights into transcriptional misregulation in disease are discussed.
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Pervasive roles of microRNAs in cardiovascular biology
Eric M. Small,Eric N. Olson +1 more
TL;DR: The wideranging functions of microRNAs in the cardiovascular system have provided new perspectives on disease mechanisms and have revealed intriguing therapeutic targets, as well as diagnostics, for a variety of cardiovascular disorders.
References
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Journal ArticleDOI
MicroRNAs: Genomics, Biogenesis, Mechanism, and Function
TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
Journal ArticleDOI
Silencing of microRNAs in vivo with ‘antagomirs’
Jan Krützfeldt,Nikolaus Rajewsky,Ravi Braich,Kallanthottathil G. Rajeev,Thomas Tuschl,Muthiah Manoharan,Markus Stoffel +6 more
TL;DR: It is shown that a novel class of chemically engineered oligonucleotides, termed ‘antagomirs’, are efficient and specific silencers of endogenous miRNA levels in mice and may represent a therapeutic strategy for silencing miRNAs in disease.
Journal ArticleDOI
Cellular and molecular mechanisms of fibrosis.
TL;DR: Current understanding of the cellular and molecular mechanisms of fibrogenesis is explored and components of the renin–angiotensin–aldosterone system (ANG II) have been identified as important regulators of fibrosis and are being investigated as potential targets of antifibrotic drugs.
Journal ArticleDOI
Transforming growth factor beta in tissue fibrosis.
Wayne A. Border,Nancy A. Noble +1 more
TL;DR: A large number of patients with progressive fibrosis have no known underlying cause of disease and the prognosis is poor, suggesting that the disease is likely to get worse as they age.
Journal ArticleDOI
Control of translation and mRNA degradation by miRNAs and siRNAs
TL;DR: Possible mechanisms by which miRNAs control translation and mRNA degradation are discussed, an emerging theme is that mi RNAs, and siRNAs to some extent, target m RNAs to the general eukaryotic machinery for mRNA degradation and translation control.
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