Plasma exosomal miRNAs involved in endothelial injury in microscopic polyangiitis patients

显微镜下多血管炎患者血浆外泌体 miRNA 参与内皮损伤

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作者:Yang Wang, Yingyu Bai, Yixin Liu, Sam Wilfried Noel, Qiushuang Yan, Huyen Pham Thi, Xuguo Sun, Wei Wei, Jun Ma, Fang Zheng

Abstract

Microscopic polyangiitis (MPA) is a systemic autoimmune disease that primarily affects the small and medium blood vessels. Endothelial injury is one of the pathological hallmarks of MPA. However, the pathogenesis for this has not yet been fully elucidated. Exosomal microRNAs (miRNAs) have recently emerged as a new molecular pattern involved in the endothelial injury in other diseases. Hence, we speculated that MPA plasma-derived exosomes (MPA-exo) could induce the endothelial injury, which was likely to be aroused by the dysregulated exosomal miRNAs in MPA. In the present study, plasma-derived exosomes were isolated and identified. MPA-exo could be internalized by human renal glomerular endothelial cells (HRGECs) in vitro and induced HRGECs injury. Subsequently, a series of differentially expressed miRNAs in MPA-exo were identified by high-throughput sequencing analysis. Further bioinformatics analysis for the target genes of these differentially expressed miRNAs showed a potential mechanism for their possible role in MPA endothelial injury. Notably, we revealed a considerable correlation between miR-185-3p, miR-125a-3p, and clinical parameters. In conclusion, the current study revealed that differentially expressed miRNAs in MPA-exo are associated with the endothelial injury. Our results suggested that these miRNAs and their target genes might be involved in the inflammation process of MPA.

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