miRNA-153-5p regulates macrophage polarization in viral myocarditis by targeting TFRC
Objective:To investigate the role of miRNA-153-5p in regulating macrophage polarization in viral myocarditis.Methods:A mouse model of viral myocarditis was established,and from which the hearts were obtained.RT-qPCR was performed to detect the expression of miRNA-153-5p in myocardial tissue,and heart tissues were stained with HE to examine the degree of inflammation.ELISA was applied to measure the serum troponin cTnI level in mice,and flow cytometry was used to detect the phenotype of infiltrating macrophages in the heart.Bone marrow-derived macrophages(BMDMs)were isolated in vitro,and then induced as M1/M2 type macrophages,overexpressed and suppressed miR-153-5p.RT-qPCR was used to determine the expression of M1/M2 markers iNOS,IL-12,TNF-α,Arg1,YM-1,and FIZZ1.Finally,bioinformatics software prediction combined with dual luciferase assay were used to verify the targeting relationship of miR-153-5p with TFRC.Results:miR-153-5p was highly expressed in the heart tissues of mice with viral myocarditis at day 7 of CVB3 infection.Inhibition of miR-153-5p expression in in vivo experiments reduced the extent of lesions and improved cardiac function in viral myocarditis mouse hearts.Inhibition of miR-153-5p expression generated polarization of mouse heart-infiltrating macrophages toward M2.In in vitro experiments,miR-153-5p expression was elevated in M1 macrophages compared to M2.Overexpression of miR-153-5p resulted in macrophage polarization toward M1,whereas inhibition of miR-153-5p expression stimulated macrophage polarization toward M2.The transferrin receptor TFRC functioned a target gene of miR-153-5p,and inhibition of miR-153-5p expression upregulated the mRNA and protein levels of TFRC.Conclusion:miRNA-153-5p can regulate the polarization of cardiac infiltrating macrophages in viral myocarditis mice by targeting TFRC.
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维普
