Time-Series transcriptome analysis reveals the miR-27a-5p-Ppm1l axis as a new pathway regulating macrophage alternative polarization after myocardial infarction

Shinichi Goto, Genki Ichihara, Yoshinori Katsumata, Seien Ko, Atsushi Anzai, Kosuke Shirakawa, Jin Endo, Masaharu Kataoka, Hidenori Moriyama, Takahiro Hiraide, Hiroki Kitakata, Takayasu Kobayashi, Keiichi Fukuda, Motoaki Sano

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

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, including Ppm1l. 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 regulating Ppm1l expression. Conclusions: Ppm1l and miR-27a-5p may be the key molecules regulating M2-like polarization, with miR-27a-5p inhibiting the M2-like polarization through downregulation of Ppm1l expression.

Original languageEnglish
Pages (from-to)929-938
Number of pages10
JournalCirculation Journal
Volume85
Issue number6
DOIs
Publication statusPublished - 2021

Keywords

  • Bone marrow-derived macrophages
  • M2
  • Micro-RNA
  • Microarray
  • PP2C

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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