Abstract
Exosomes are natural carriers of biological macromolecules that are involved in the pathogenesis of a wide variety of inflammatory diseases. The purpose of this study was to investigate the role of exosomes derived from injured endometrial epithelial cells (EECs) in the development of endometritis. We isolated exosomes derived from LPS-injured EECs and identified these exosomes as proinflammatory mediators that can be internalized by macrophages and thus induce proinflammatory macrophage activation. We further found that miR-331 expression was sharply downregulated in exosomes derived from LPS-injured EECs and that macrophages treated with these exosomes also presented a lower level of miR-331. Importantly, the pathogenic role of exosomal miR-331 in promoting endometrial inflammation was revealed by the ability of adoptively transferred EECs-derived exosomes to cause macrophage activation, and this was reversed by miR-331 overexpression. Mechanistically, overexpression of miR-331 in macrophages mitigated NF-κB p65 phosphorylation by inhibiting the Notch1/IKKα pathway, which in turn curbed macrophage activation. In vivo assays further unveiled that miR-331 expression is negatively correlated with proinflammatory macrophage activation and that miR-331 upregulation markedly slowed disease progression in mice with endometritis. The exosome/miR-331/Notch1 axis plays a critical pathological role in endometrial inflammation, representing a new therapeutic target for endometritis.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: International Journal of Biological Macromolecules
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.