Key result
Cardiomyocyte exosomal miR-146a-5p drives M1 macrophage inflammation but exerts TRAF6-mediated anti-inflammatory effects.
Why the study?
The effect of cardiomyocyte-derived exosomal miR-146a-5p on macrophage polarization and activation had not yet been elucidated.
Answers are grounded in this paper and cite their sources.
Cardiomyocyte-derived exosomal miR-146a-5p modulates macrophage polarization and exerts anti-inflammatory effects by targeting TRAF6, highlighting a potential therapeutic target for myocardial infarction.
Myocardial infarction arises from an excessive or prolonged inflammatory response, leading to ventricular remodeling or impaired cardiac function. Macrophages exhibit different polarization types associated with inflammation both at steady state and after myocardial infarction. Exosomal miR-146a-5p has been identified as an important molecule in the cardiovascular field in recent years. However, the effect of cardiomyocyte-derived exosomal miR-146a-5p on macrophages has not yet been elucidated. Initially, we found that exosomes with low expression of miR-146a-5p derived from myocardial infarction tissues modulated macrophage polarization. To determine whether cardiomyocyte-derived exosomal miR-146a-5p mediated macrophage polarization, we treated macrophages with exosomes rich in miR-146a-5p collected from neonatal mouse cardiomyocytes. The effects of exosomal miR-146a-5p on macrophage polarization were measured using RT-qPCR, transwell assays, and western blotting. The results showed that the increased expression of miR-146a-5p promoted M1 macrophage polarization, inhibited M2 macrophage polarization, and increased the expression of VEGFA. However, the decreased expression of exosomalmiR-146a-5p showed the opposite trends. Interestingly, in contrast to treatment with the solitary miR-146a-5p mimic, exosomal miR-146a-5p derived from neonatal mouse cardiomyocytes reduced TNFα and iNOS expression. In addition, when macrophages were activated by the miR-146a-5p mimic or exosomal miR-146a-5p, the expression of TNF receptor-associated factor 6 (TRAF6), a target gene of miR-146a-5p, was reduced significantly. Taken together, these findings indicate that exosomal miR-146a-5p derived from cardiomyocytes could stimulate M1 macrophage polarization to induce an inflammatory reaction, while targeting TRAF6, exerting an anti-inflammatory effect. Exosomal miR-146a-5p plays important roles in macrophages, illuminating a novel potential therapeutic target in myocardial infarction.
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Chen et al. (2022) studied Myocardial infarction. Cardiomyocyte-derived exosomal miR-146a-5p vs. Decreased expression / solitary miR-146a-5p mimic was evaluated on Macrophage polarization and activation. Cardiomyocyte-derived exosomal miR-146a-5p stimulated M1 macrophage polarization to induce inflammation while simultaneously targeting TRAF6 to exert an anti-inflammatory effect.
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