MicroRNA-93 may control vascular endothelial growth factor A in circulating peripheral blood mononuclear cells in acute Kawasaki disease
MicroRNA-93 may control vascular endothelial growth factor A in circulating peripheral blood mononuclear cells in acute Kawasaki disease
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DOI：
10.1038/pr.2016.93
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发表时间：
2016-09-01
影响因子：
3.6
通讯作者：
Ichida, Fukiko
中科院分区：
文献类型：
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作者：
Saito, Kazuyoshi;Nakaoka, Hideyuki;Ichida, Fukiko
背景：川崎病(KD)是最常见的全身性血管炎综合征，主要累及中型动脉，尤其是冠状动脉。虽然KD可能与免疫学问题有关，但microRNAs(MiRs)的参与还没有完全描述。我们对急性KD患者和对照组的外周血单个核细胞(PBMC)进行了miR和mRNA微阵列分析。结果：急性发热期miR-182、miR-296-5p显著升高，退热期尤其是难治性KD患者miR-93、miR-145-5p、miR-145-3p、miR-150-3p显著升高。先前报道受miR-93控制的血管内皮生长因子A(VEGFA)mRNA的表达在发热期显著升高，治疗后恢复正常，与miR-93的表达呈负相关。此外，血浆中VEGF-A水平与PBMC VEGFA基因表达呈正相关。结论：多个MIR对KD急性期具有高度特异性，可能参与调节KD相关基因的表达。特别是miR-93可能参与调节血管内皮生长因子-A的表达，参与急性川崎病动脉炎的发病机制。
BACKGROUND: Kawasaki disease (KD) is the most common systemic vasculitis syndrome primarily affecting medium-sized arteries, particularly the coronary arteries. Though KD may be associated with immunological problems, the involvement of microRNAs (miRs) has not been fully described.METHODS: We enrolled 23 KD patients and 12 controls. We performed miR and mRNA microarray analysis of peripheral blood mononuclear cells (PBMCs) isolated from acute KD patients and controls. Continuously, we measured specific miRs, mRNA and the expression of proteins by using reverse-transcriptase PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA).RESULTS: We identified strikingly high levels of miR-182 and miR-296-5p during the acute febrile phase, and of miR-93, miR-145-5p, miR-145-3p, and miR-150-3p in the defervescence stage, especially in refractory KD patients. The expression of vascular endothelial growth factor A (VEGFA) mRNA, previously reported to be controlled by miR-93, was significantly elevated during the febrile phase and normalized upon treatment, negatively correlating with the expression of miR-93. Further, plasma levels of VEGF-A correlated with PBMC VEGFA mRNA expression.CONCLUSION: Several miRs are highly specific to the acute phase of KD, and may participate in regulating the expression of genes in pathways associated with KD. In particular, miR-93 may participate in regulating expression of VEGF-A and contribute to the pathogenesis of arteritis in acute KD.