Changes in the Expression of miR-34a and its Target Genes Following Spinal Cord Injury In Rats.
Changes in the Expression of miR-34a and its Target Genes Following Spinal Cord Injury In Rats.
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大鼠脊髓损伤后miR-34a及其靶基因表达的变化
DOI：
10.12659/msm.900893
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发表时间：
2016-10-25
期刊：
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Chen Y;Cao S;Xu P;Han W;Shan T;Pan J;Lin W;Chen X;Wang X
背景DNA芯片实验结果表明，脊髓损伤后miR-34S的表达发生了显著变化。本研究旨在检测miR-34s及其靶基因在脊髓损伤急性期和亚急性期的表达变化。材料/方法采用LFB髓鞘染色方法，观察大鼠脊髓挫伤后脊髓大体形态的变化。采用定量聚合酶链式反应技术检测miR-34S及其靶基因在脊髓损伤急性期和亚急性期的表达变化。利用模拟技术进一步证实miR-34a对潜在靶基因的调控作用。结果miR-34a在脊髓损伤后即刻开始下降，并持续21d。MiR-34c的表达水平在脊髓损伤后第1天开始下降，并持续到第14天，脊髓损伤后miR-34b的表达水平无明显变化。双重免疫荧光和原位杂交结果表明，miR-34a在脊髓神经元中高表达。根据我们的生物信息学分析，我们推测miR-34a可能通过调控靶基因Notch1参与脊髓损伤后细胞的凋亡，并可能分别通过调控候选基因CSF1R和PDGFRα参与炎症反应和胶质瘢痕的形成。脊髓损伤后候选基因CSF1R和PDGFRNotch1的α表达水平基本一致。该模拟技术进一步证实了miR-34a对上述靶基因的调控作用。结论我们推测miR-34a和miR-34c可能参与脊髓损伤后多方面的细胞生物学活动。特别是，MIR-34a可能通过分别调控靶基因Notch1和候选靶基因CSF1R和PDGFRα参与细胞凋亡、炎症反应和胶质瘢痕形成。
Background Results from DNA microarray experiments have shown that the expression of miR-34s undergoes significant changes following spinal cord injury (SCI). The present study was designed to detect changes in the expression of miR-34s and its target genes during the acute and sub-acute stages of SCI. Material/Methods Luxol fast blue (LFB) staining for myelin was used to observe the differences in the general morphology of the spinal cord after SCI in a contusion model in rats. qPCR was carried out to determine the expression variation of miR-34s and its target genes during the acute and sub-acute stages of SCI. The mimic technique was used to further confirm the regulatory effect of miR-34a on the potential target genes. Results The expression level of miR-34a decreased immediately after SCI and persisted for 21 days after SCI. The expression level of miR-34c began decreasing at day 1 after SCI and persisted until day 14. The expression level of miR-34b did not undergo significant change after SCI. The results of double immunofluorescence and in-situ hybridization suggested that miR-34a was highly expressed in spinal cord neurons. Based on our bioinformatics analysis, we postulated that miR-34a might participate in post-SCI cell apoptosis by regulating the target gene Notch1, and likely participated in the inflammatory response and glial scar formation by regulating the candidate genes Csf1r and PDGFRα, respectively. The expression levels of the candidate genes Csf1r and PDGFRα were consistent with Notch1 after SCI. The mimic technique further confirmed the regulatory effect of miR-34a on the aforementioned target genes. Conclusions We postulate that miR-34a and miR-34c might participate in multiple aspects of cytobiological activities following SCI. MiR-34a in particular may participate in cell apoptosis, inflammatory response, and glial scar formation by regulating the target gene Notch1 and candidate target genes Csf1r and PDGFRα respectively.
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影响因子：
4.8
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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创伤性脊髓损伤后的microRNA表达改变。
影响因子：
5.3
作者：
Liu, Nai-Kui;Wang, Xiao-Fei;Lu, Qing-Bo;Xu, Xiao-Ming
通讯作者：
Xu, Xiao-Ming