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内皮细胞微囊泡中包裹的 microRNA-145-5p 和 microRNA-320a 促进急性川崎病血管炎的进展。

MicroRNA-145-5p and microRNA-320a encapsulated in endothelial microparticles contribute to the progression of vasculitis in acute Kawasaki Disease.

机构信息

Department of Pediatrics, Faculty of Medicine, University of Toyama, Toyama, Japan.

Department of Pathology, Faculty of Medicine, University of Toyama, Toyama, Japan.

出版信息

Sci Rep. 2018 Jan 17;8(1):1016. doi: 10.1038/s41598-018-19310-4.

Abstract

Kawasaki Disease (KD) is an acute inflammatory disease that takes the form of systemic vasculitis. Endothelial microparticles (EMPs) have been recognized as an important transcellular delivery system. We hypothesized whether EMPs are involved in vasculitis in acute KD. Fifty patients with acute KD were enrolled, divided into two subgroups: those with coronary artery lesions (CAL) (n = 5) and those without CAL (NCAL) (n = 45). EMPs were measured using flow cytometry, and microRNA (miR) expression profiling was performed by microRNA array. The percentage of EMPs in acute KD was significantly higher than in controls (P < 0.0001). EMPs in patients with CAL rapidly increased after the initial treatment, and was significantly higher than those in NCAL (P < 0.001). In patients with CAL, we identified 2 specific miRs encapsulated in EMPs, hsa-miR-145-5p and hsa-miR-320a, which are predicted to affect monocyte function using in silico analysis, and were demonstrated to upregulate inflammatory cytokine mRNAs in THP-1 monocytes. In situ hybridization confirmed that hsa-miR-145-5p was preferentially expressed in CAL. EMPs may serve as a sensitive marker for the severity of vasculitis in acute KD. Moreover, these 2 specific miRs encapsulated in EMPs might be involved in inflammatory cytokine regulation and the pathogenesis of vasculitis in acute KD.

摘要

川崎病(KD)是一种全身性血管炎的急性炎症性疾病。内皮细胞微颗粒(EMPs)已被认为是一种重要的细胞间传递系统。我们假设 EMP 是否参与急性 KD 的血管炎。

纳入 50 例急性 KD 患者,分为两组:伴有冠状动脉损伤(CAL)组(n=5)和无 CAL 组(NCAL)(n=45)。采用流式细胞术测量 EMPs,采用 miRNA 芯片进行 miRNA 表达谱分析。急性 KD 患者的 EMPs 百分比明显高于对照组(P<0.0001)。CAL 患者在初始治疗后 EMPs 迅速增加,明显高于 NCAL 组(P<0.001)。在 CAL 患者中,我们鉴定出 2 种特定的 miR,hsa-miR-145-5p 和 hsa-miR-320a,其通过计算机分析预测会影响单核细胞功能,并证明可上调 THP-1 单核细胞中炎症细胞因子的 mRNA。原位杂交证实 hsa-miR-145-5p 在 CAL 中优先表达。EMP 可能是急性 KD 血管炎严重程度的敏感标志物。此外,这些包裹在 EMP 中的 2 种特定的 miR 可能参与急性 KD 中炎症细胞因子的调节和血管炎的发病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08fa/5772486/ade3a41f0384/41598_2018_19310_Fig1_HTML.jpg

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