Long noncoding RNA regulates cardiac fibrosis.

Mol Ther Nucleic Acids

Department of Cardiology, Provincial Key Lab of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.

Published: March 2021

AI Article Synopsis

  • Cardiac fibrosis is a serious condition that develops in most heart diseases, leading to decreased heart function and potential heart failure; the study focuses on understanding the role of long noncoding RNAs (lncRNAs) in this process.
  • Researchers identified a specific lncRNA called AK048087, which is significantly upregulated after myocardial infarction (heart attack) and plays a crucial role in cardiac fibroblast activation and fibrosis regulation.
  • The findings suggest that targeting lncRNA AK048087 could be a promising therapeutic approach to prevent cardiac fibrosis and improve heart function in patients with heart disease.

Article Abstract

Cardiac fibrosis occurs in most cardiac diseases, which reduces cardiac muscle compliance, impairs both systolic and diastolic heart function and, ultimately, leads to heart failure. Long noncoding RNAs (lncRNAs) have recently emerged as important regulators of a variety of biological processes; however, little is known about the expression and function of lncRNAs in cardiac fibrosis. Using unbiased transcriptome profiling in a mouse model of myocardial infarction (MI), we identified a cardiac fibroblast-enriched lncRNA (AK048087) named cardiac fibroblast-associated transcript (), which is significantly elevated after MI. Silencing expression by small interfering RNAs (siRNAs) or lentiviral short hairpin RNAs (shRNAs) resulted in suppression of fibrosis-related gene expression and transdifferentiation of myofibroblasts into cardiac fibroblasts. Depletion of by lentiviral shRNAs in mouse hearts significantly attenuated cardiac fibrosis induced by MI or isoproterenol-infusion. Importantly, inhibition of ameliorated cardiac function following cardiac injury. RNA pull-down followed by mass spectrometry analyses identified COTL1 (coactosin-like 1) as one of the interacting proteins. Mechanistically, competitively inhibits the COTL1 interaction with TRAP1 (transforming growth factor-β receptor-associated protein 1), which enhances TGF-β signaling by augmenting SMAD2/SMAD4 complex formation. Therefore, our study identifies as a novel cardiac fibroblast-enriched lncRNA that regulates cardiac fibroblast activation in response to pathophysiological stress. could serve as a potential therapeutic target for the prevention of cardiac fibrosis and cardiac diseases.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787992PMC
http://dx.doi.org/10.1016/j.omtn.2020.11.013DOI Listing

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