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缺氧缺血诱导的发育中大鼠少突胶质前体细胞中的 microRNA 改变。

MicroRNA Alteration in Developing Rat Oligodendrocyte Precursor Cells Induced by Hypoxia-Ischemia.

机构信息

Department of Pediatrics, West China Second University Hospital.

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education.

出版信息

J Neuropathol Exp Neurol. 2019 Oct 1;78(10):900-909. doi: 10.1093/jnen/nlz071.

Abstract

microRNAs (miRNAs) are involved in the pathogenesis of white matter injury (WMI). However, their roles in developing rat brains under hypoxia-ischemia (HI) insult remain unknown. Here, we examined the expression profiles of miRNAs in oligodendrocyte precursor cells using microarray analysis. We identified 162 miRNAs and only 6 were differentially regulated in HI compared with sham. Next, we used these 6 miRNAs and 525 extensively changed coding genes (fold change absolute: FC(abs) ≥2, p < 0.05) to establish the coexpression network, the result revealed that only 3 miRNAs (miR-142-3p, miR-466b-5p, and miR-146a-5p) have differentially expressed targeted mRNAs. RT-PCR analysis showed that the expression of the miRNAs was consistent with the microarray analysis. Further gene ontology and KEGG pathway analysis of the targets of these 3 miRNAs indicated that they were largely associated with neural activity. Furthermore, we found that 2 of the 3 miRNAs, miR-142-3p, and miR-466b-5p, have the same target gene, Capn6, an antiapoptotic gene that is tightly regulated in the pathogenesis of neurological diseases. Collectively, we have shown that a number of miRNAs change in oligodendrocyte precursor cells in response to HI insult in developing brains, and miR-142-3p/miR-466b-5p/Capn6 pathway might affect the pathogenesis of WMI, providing us new clues for the diagnosis and therapy for WMI.

摘要

微小 RNA(miRNAs)参与了脑白质损伤(WMI)的发病机制。然而,它们在缺氧缺血(HI)损伤下发育中的大鼠大脑中的作用尚不清楚。在这里,我们使用微阵列分析检查了少突胶质前体细胞中 miRNA 的表达谱。我们鉴定了 162 个 miRNA,只有 6 个在 HI 与假手术相比时存在差异调节。接下来,我们使用这 6 个 miRNA 和 525 个广泛变化的编码基因(倍数变化绝对值:FC(abs)≥2,p<0.05)建立了共表达网络,结果表明只有 3 个 miRNA(miR-142-3p、miR-466b-5p 和 miR-146a-5p)具有差异表达的靶向 mRNAs。RT-PCR 分析显示 miRNA 的表达与微阵列分析一致。对这 3 个 miRNA 的靶基因进行进一步的基因本体和 KEGG 通路分析表明,它们主要与神经活性相关。此外,我们发现这 3 个 miRNA 中的 2 个,miR-142-3p 和 miR-466b-5p,具有相同的靶基因 Capn6,这是一个在神经疾病发病机制中受到严格调控的抗凋亡基因。总的来说,我们已经表明,在发育中的大脑中,HI 损伤会导致少突胶质前体细胞中大量 miRNA 发生变化,miR-142-3p/miR-466b-5p/Capn6 通路可能影响 WMI 的发病机制,为 WMI 的诊断和治疗提供了新的线索。

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