Time-Series Transcriptome Analysis Reveals the miR-27a-5p-Ppm1l Axis as a New Pathway Regulating Macrophage Alternative Polarization After Myocardial Infarction

被引：6

作者：

Goto, Shinichi ^{[1
]}

Ichihara, Genki ^{[1
]}

Katsumata, Yoshinori ^{[1
,2
]}

Ko, Seien ^{[1
]}

Anzai, Atsushi ^{[1
]}

Shirakawa, Kohsuke ^{[1
]}

Endo, Jin ^{[1
]}

Kataoka, Masaharu ^{[1
]}

Moriyama, Hidenori ^{[1
]}

Hiraide, Takahiro ^{[1
]}

Kitakata, Hiroki ^{[1
]}

Kobayashi, Takayasu ^{[3
]}

Fukuda, Keiichi ^{[1
]}

Sano, Motoaki ^{[1
]}

机构：

[1] Keio Univ, Dept Cardiol, Sch Med, Tokyo, Japan

[2] Keio Univ, Inst Integrated Sports Med, Sch Med, Tokyo, Japan

[3] Tohoku Univ, Ctr Gene Res, Sendai, Miyagi, Japan

来源：

CIRCULATION JOURNAL | 2021年 / 85卷 / 06期

关键词：

Bone marrow-derived macrophages; Microarray; M2; Micro-RNA; PP2C; INFLAMMATORY RESPONSE; REPAIR; MICRORNAS; ACCUMULATION; PHOSPHATASE; ACTIVATION; EXPRESSION; MECHANISM; MONOCYTE; PROTEIN;

D O I：

10.1253/circj.CJ-20-0783

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：929 / +

页数：22

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