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

MicroRNA-145-5p and microRNA-320a encapsulated in endothelial microparticles contribute to the progression of vasculitis in acute Kawasaki Disease.
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MicroRNA-145-5P和MicroRNA-320A封装在内皮微粒中,有助于急性川崎疾病中的血管炎进展。

DOI:
10.1038/s41598-018-19310-4
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发表时间:
2018-01-17
期刊:
影响因子:
4.6
通讯作者:
Ichida F
Ichida F
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Nakaoka H;Hirono K;Yamamoto S;Takasaki I;Takahashi K;Kinoshita K;Takasaki A;Nishida N;Okabe M;Ce W;Miyao N;Saito K;Ibuki K;Ozawa S;Adachi Y;Ichida F

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川崎是一种以全身性血管炎为主要表现的急性炎症性疾病。内皮微粒(EMPs)是一种重要的跨细胞转运系统。我们假设是否EMP参与急性KD的血管炎。入选50例急性KD患者,分为两个亚组:有冠状动脉病变(CAL)(n = 5)和无CAL(NCAL)(n = 45)。使用流式细胞术测量EMP,并通过microRNA阵列进行microRNA(miR)表达谱分析。急性期川崎病患儿EMPs阳性率明显高于对照组(P < 0.0001)。CAL组治疗后EMPs迅速升高,且明显高于NCAL组(P < 0.001)。在CAL患者中,我们鉴定了包封在EMP中的2种特异性miR,hsa-miR-145- 5 p和hsa-miR-320 a,使用计算机模拟分析预测其影响单核细胞功能,并且证明其上调THP-1单核细胞中的炎性细胞因子mRNA。原位杂交证实hsa-miR-145- 5 p在CAL中优先表达,EMPs可作为判断急性KD血管炎严重程度的敏感指标。此外,这2种特异性miR包封在EMP中,可能参与炎症细胞因子的调节和急性KD血管炎的发病机制。
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.
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