The long noncoding RNA Wisper controls cardiac fibrosis and remodeling.

Details

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State: Public
Version: Author's accepted manuscript
Serval ID
serval:BIB_21B9C22B9E14
Type
Article: article from journal or magazin.
Collection
Publications
Title
The long noncoding RNA Wisper controls cardiac fibrosis and remodeling.
Journal
Science translational medicine
Author(s)
Micheletti R., Plaisance I., Abraham B.J., Sarre A., Ting C.C., Alexanian M., Maric D., Maison D., Nemir M., Young R.A., Schroen B., González A., Ounzain S., Pedrazzini T.
ISSN
1946-6242 (Electronic)
ISSN-L
1946-6234
Publication state
Published
Issued date
21/06/2017
Peer-reviewed
Oui
Volume
9
Number
395
Pages
395
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Long noncoding RNAs (lncRNAs) are emerging as powerful regulators of cardiac development and disease. However, our understanding of the importance of these molecules in cardiac fibrosis is limited. Using an integrated genomic screen, we identified javax.xml.bind.JAXBElement@1d337375 (Wisp2 super-enhancer-associated RNA) as a cardiac fibroblast-enriched lncRNA that regulates cardiac fibrosis after injury. javax.xml.bind.JAXBElement@690a7099 expression was correlated with cardiac fibrosis both in a murine model of myocardial infarction (MI) and in heart tissue from human patients suffering from aortic stenosis. Loss-of-function approaches in vitro using modified antisense oligonucleotides (ASOs) demonstrated that javax.xml.bind.JAXBElement@a00ce9a is a specific regulator of cardiac fibroblast proliferation, migration, and survival. Accordingly, ASO-mediated silencing of javax.xml.bind.JAXBElement@35b3fd8e in vivo attenuated MI-induced fibrosis and cardiac dysfunction. Functionally, javax.xml.bind.JAXBElement@339d9896 regulates cardiac fibroblast gene expression programs critical for cell identity, extracellular matrix deposition, proliferation, and survival. In addition, its association with TIA1-related protein allows it to control the expression of a profibrotic form of lysyl hydroxylase 2, implicated in collagen cross-linking and stabilization of the matrix. Together, our findings identify javax.xml.bind.JAXBElement@929a8c4 as a cardiac fibroblast-enriched super-enhancer-associated lncRNA that represents an attractive therapeutic target to reduce the pathological development of cardiac fibrosis in response to MI and prevent adverse remodeling in the damaged heart.

Keywords
Cardiomyopathies/genetics, Cardiomyopathies/pathology, Fibroblasts/metabolism, Fibroblasts/pathology, Fibrosis/genetics, Fibrosis/pathology, Humans, RNA, Long Noncoding/genetics, RNA, Long Noncoding/physiology, Ventricular Remodeling
Pubmed
Web of science
Open Access
Yes
Create date
06/07/2017 18:47
Last modification date
20/08/2019 13:58
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