Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Basic Science
Time-Series Transcriptome Analysis Reveals the miR-27a-5p-Ppm1l Axis as a New Pathway Regulating Macrophage Alternative Polarization After Myocardial Infarction
Shinichi GotoGenki IchiharaYoshinori KatsumataSeien KoAtsushi AnzaiKohsuke ShirakawaJin EndoMasaharu KataokaHidenori MoriyamaTakahiro HiraideHiroki KitakataTakayasu KobayashiKeiichi FukudaMotoaki Sano
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Supplementary material

2021 Volume 85 Issue 6 Pages 929-938

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Abstract

Background:Timely differentiation of monocytes into M2-like macrophages is important in the cardiac healing process after myocardial infarction (MI), but molecular mechanisms governing M2-like macrophage differentiation at the transcriptional level after MI have not been fully understood.

Methods and Results:A time-series microarray analysis of mRNAs and microRNAs in macrophages isolated from the infarcted myocardium was performed to identify the microRNAs involved in regulating the process of differentiation to M2-like macrophages. Correlation analysis revealed 7 microRNAs showing negative correlations with the progression of polarity changes towards M2-like subsets. Next, correlation coefficients for the changes in expression of mRNAs and miRNAs over time were calculated for all combinations. As a result, miR-27a-5p was extracted as a possible regulator of the largest number of genes in the pathway for the M2-like polarization. By selecting mouse mRNAs and human mRNAs possessing target sequences of miR-27a-5p and showing expression patterns inversely correlated with that of miR-27a-5p, 8 potential targets of miR-27a-5p were identified, includingPpm1l. Using the mouse bone marrow-derived macrophages undergoing differentiation into M2-like subsets by interleukin 4 stimulation, we confirmed that miR-27a-5p suppressed M2-related genes by negatively regulatingPpm1lexpression.

Conclusions:Ppm1land miR-27a-5p may be the key molecules regulating M2-like polarization, with miR-27a-5p inhibiting the M2-like polarization through downregulation ofPpm1lexpression.

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© 2021, THE JAPANESE CIRCULATION SOCIETY

This article is licensed under a Creative Commons [Attribution-NonCommercial-NoDerivatives 4.0 International] license.
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