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Combined high-throughput library screening and next generation RNA sequencing uncover microRNAs controlling human cardiac fibroblast biology
Schimmel, Katharina Stojanović, Stevan D. Huang, Cheng Kai Jung, Mira Meyer, Martin H. Xiao, Ke Grote-Levi, Lea Bär, Christian Pfanne, Angelika Mitzka, Saskia
Schimmel, Katharina
Stojanović, Stevan D.
Huang, Cheng Kai
Jung, Mira
Meyer, Martin H.
Xiao, Ke
Grote-Levi, Lea
Bär, Christian
Pfanne, Angelika
Mitzka, Saskia
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2021-01-01
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Abstract
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.
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J Mol Cell Cardiol. 2020 Oct 28;150:91-100. doi: 10.1016/j.yjmcc.2020.10.008. Epub ahead of print.
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en
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00222828
EISSN
10958584
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European Research Council
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Attribution-NonCommercial-ShareAlike 4.0 International