miR-190a-5p targeting the C/EBPα-PU.1 pathway promotes the polarization of bone-marrow-derived macrophages from M1-type to M2-type_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

YANG Lei , XUE Song , WANG Yaxiang ,  LIAN Feng

Department of Cardiovascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, P. R. China;

Corresponding author：

LIAN Feng, Email: dr.lianfeng@hotmail.com

Keywords：

miR-190a-5p; macrophages; C/EBPα; polarization; experiment

DOI：

10.7507/1007-4848.202012109

Video：

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Objective To investigate the effect of miR-190a-5p on the polarization of bone-marrow-derived macrophage (BMDM) induced by lipopolysaccharides to M1- and M2-types.Methods BMDM (M1-type) induced by bacterial lipopolysaccharide was a M1 group. The macrophage M1-type interfered with negative control miRNA mimics was a NC group. miR-190a-5p mimics interfered with the M1-type of macrophages in the miR-190a-5p group. Morphological changes of macrophages were observed under a microscope, and the proportion of M2-type macrophages (CD206+, F4/80) was detected by flow cytometry. The mRNA expression levels of argininase-1 (Arg1), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), target gene C/EBPα and PU.1 were detected by fluorescence quantitative PCR to verify whether C/EBPα and PU.1 were potential target genes of miR-190a-5p. The expression of pathway proteins C/EBPα and PU.1 were detected by Western blotting.Results After miR-190a-5p mimics interfered with macrophage M1-type, the antenna of macrophages elongated and showed long cord M2-type cell morphological characteristics. miR-190a-5p mimics interfered with M1-type macrophages for 24 h, and the percentage of M2-type macrophages increased significantly (P<0.05). Effects of miR-190a-5p simulator on mRNA expression levels of M1-type macrophages included: the expression of iNOS and TNF-α was significantly decreased (P<0.05), the expression of Arg1 marked by M2 macrophages was significantly increased (P<0.05), and the mRNA expression levels of target genes C/EBPα and PU.1 were significantly decreased (P<0.05). Western blotting results showed that the overexpression of miR-190a-5p significantly inhibited the protein expressions of C/EBPα and PU.1, while the miR-190a-5p inhibitor increased the expressions of both proteins.Conclusion miR-190a-5p can promote the polarization of BMDM from M1-type to M2-type.

Citation： YANG Lei, XUE Song, WANG Yaxiang, LIAN Feng. miR-190a-5p targeting the C/EBPα-PU.1 pathway promotes the polarization of bone-marrow-derived macrophages from M1-type to M2-type. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2022, 29(8): 1042-1048. doi: 10.7507/1007-4848.202012109 Copy

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1. Murray PJ. Macrophage polarization. Annu Rev Physiol, 2017, 10(79): 541-566.
2. Wang N, Liang H, Zen K. Molecular mechanisms that influence the macrophage M1-M2 polarization balance. Front Immunol, 2014, 5: 614.
3. Liu YC, Zou XB, Chai YF, et al. Macrophage polarization in inflammatory diseases. Int J Biol Sci, 2014, 10(5): 520-529.
4. Funes SC, Rios M, Escobar-Vera J, et al. Implications of macrophage polarization in autoimmunity. Immunology, 2018, 154(2): 186-195.
5. Shapouri-Moghaddam A, Mohammadian S, Vazini H, et al. Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol, 2018, 233(9): 6425-6440.
6. Wang Y, Smith W, Hao D, et al. M1 and M2 macrophage polarization and potentially therapeutic naturally occurring compounds. Int Immunopharmacol, 2019, 70: 459-466.
7. Locati M, Curtale G, Mantovani A. Diversity, mechanisms, and significance of macrophage plasticity. Annu Rev Pathol, 2020, 15: 123-147.
8. Mohammadi A, Blesso CN, Barreto GE, et al. Macrophage plasticity, polarization and function in response to curcumin, a diet-derived polyphenol, as an immunomodulatory agent. J Nutr Biochem, 2019, 66: 1-6.
9. Khan A, Singh VK, Hunter RL, et al. Macrophage heterogeneity and plasticity in tuberculosis. J Leukoc Biol, 2019, 106(2): 275-282.
10. El Kasmi KC, Stenmark KR. Contribution of metabolic reprogramming to macrophage plasticity and function. Semin Immunol, 2015, 27(4): 267-275.
11. Gharib SA, McMahan RS, Eddy WE, et al. Transcriptional and functional diversity of human macrophage repolarization. J Allergy Clin Immunol, 2019, 143(4): 1536-1548.
12. Boscá L, González-Ramos S, Prieto P, et al. Metabolic signatures linked to macrophage polarization: From glucose metabolism to oxidative phosphorylation. Biochem Soc Trans, 2015, 43(4): 740-744.
13. Viola A, Munari F, Sánchez-Rodríguez R, et al. The metabolic signature of macrophage responses. Front Immunol, 2019, 10: 1462.
14. Li H, Jiang T, Li MQ, et al. Transcriptional regulation of macrophages polarization by microRNAs. Front Immunol, 2018, 9: 1175.
15. Ma S, Liu M, Xu Z, et al. A double feedback loop mediated by microRNA-23a/27a/24-2 regulates M1 versus M2 macrophage polarization and thus regulates cancer progression. Oncotarget, 2016, 7(12): 13502-13519.
16. Lin L, Lin H, Wang L, et al. miR-130a regulates macrophage polarization and is associated with non-small cell lung cancer. Oncol Rep, 2015, 34(6): 3088-3096.
17. Essandoh K, Li Y, Huo J, et al. MiRNA-mediated macrophage polarization and its potential role in the regulation of inflammatory response. Shock, 2016, 46(2): 122-31.
18. Song J, Yang S, Yin R, et al. MicroRNA-181a regulates the activation of the NLRP3 inflammatory pathway by targeting MEK1 in THP-1 macrophages stimulated by ox-LDL. J Cell Biochem, 2019, 120(8): 13640-13650.
19. Park JE, Dutta B, Tse SW, et al. Hypoxia-induced tumor exosomes promote M2-like macrophage polarization of infiltrating myeloid cells and microRNA-mediated metabolic shift. Oncogene, 2019, 38(26): 5158-5173.
20. Mann M, Mehta A, Zhao JL, et al. An NF-κB-microRNA regulatory network tunes macrophage inflammatory responses. Nat Commun, 2017, 8(1): 851.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

miR-190a-5p targeting the C/EBPα-PU.1 pathway promotes the polarization of bone-marrow-derived macrophages from M1-type to M2-type

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