Combined high-throughput library screening and next generation RNA sequencing uncover microRNAs controlling human cardiac fibroblast biology
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Authors
Schimmel, KatharinaStojanović, Stevan D.
Huang, Cheng Kai
Jung, Mira
Meyer, Martin H.
Xiao, Ke
Grote-Levi, Lea
Bär, Christian
Pfanne, Angelika
Mitzka, Saskia
Just, Annette
Geffers, Robert
Bock, Katharina
Kenneweg, Franziska
Kleemiß, Felix
Falk, Christine S.
Fiedler, Jan
Thum, Thomas
Issue Date
2021-01-01
Metadata
Show full item recordAbstract
Background: Myocardial fibrosis is a hallmark of the failing heart, contributing to the most common causes of deaths worldwide. Several microRNAs (miRNAs, miRs) controlling cardiac fibrosis were identified in recent years; however, a more global approach to identify miRNAs involved in fibrosis is missing. Methods and results: Functional miRNA mimic library screens were applied in human cardiac fibroblasts (HCFs) to identify annotated miRNAs inducing proliferation. In parallel, miRNA deep sequencing was performed after subjecting HCFs to proliferating and resting stimuli, additionally enabling discovery of novel miRNAs. In-depth in vitro analysis confirmed the pro-fibrotic nature of selected, highly conserved miRNAs miR-20a-5p and miR-132-3p. To determine downstream cellular pathways and their role in the fibrotic response, targets of the annotated miRNA candidates were modulated by synthetic siRNA. We here provide evidence that repression of autophagy and detoxification of reactive oxygen species by miR-20a-5p and miR-132-3p explain some of their pro-fibrotic nature on a mechanistic level. Conclusion: We here identified both miR-20a-5p and miR-132-3p as crucial regulators of fibrotic pathways in an in vitro model of human cardiac fibroblast biology.Citation
J Mol Cell Cardiol. 2020 Oct 28;150:91-100. doi: 10.1016/j.yjmcc.2020.10.008. Epub ahead of print.Affiliation
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.Publisher
ElsevierPubMed ID
33127387Type
ArticleLanguage
enISSN
00222828EISSN
10958584Sponsors
European Research Councilae974a485f413a2113503eed53cd6c53
10.1016/j.yjmcc.2020.10.008
Scopus Count
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- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
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