Serum miRNAs are potential biomarkers for the detection of disc degeneration, among which miR-26a-5p suppresses Smad1 to regulate disc homeostasis
Serum miRNAs are potential biomarkers for the detection of disc degeneration, among which miR-26a-5p suppresses Smad1 to regulate disc homeostasis
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DOI：
10.1111/jcmm.14544
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发表时间：
2019-07-23
影响因子：
5.3
通讯作者：
Huang, Jian
中科院分区：
文献类型：
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作者：
Fan, Yunshan;Zhao, Lan;Huang, Jian
椎间盘退变是一种常见的临床情况，损伤的椎间盘会导致慢性疼痛；然而，目前还没有一种实验室诊断方法来检测它。由于循环中的miRNAs具有作为生物标志物的潜力，其在椎间盘退变中的应用尚未被探索。在这里，我们从小鼠椎间盘退变模型中制备了血清miRNAs，并进行了miRNA-Seq和定量PCR来表征与椎间盘退变相关的miRNAs。我们鉴定了三个miRNAs，包括miR-26a-5p、miR-122-5p和miR-215-5p，它们在椎间盘退变的发病机制中经历了扰动。特别是，在椎间盘退变模型中，与损伤前或与同龄但未发生退变的正常对照组相比，血清中miR-26a-5p的水平稳步上升，而miR-122-5p和miR-215-5p在损伤后的样本中的表达低于未手术的相应样本。此外，我们还发现miR-26a-5p靶向于Smad1的表达，而Smad1负调控盘细胞中Vegfa的表达，从而促进了盘的退变。综上所述，我们建立了一种一致的方法来分析循环中的miRNAs，并将多个miRNAs确定为有希望的椎间盘退变的生物标志物，其中miR-26a-5p通过靶向Smad1信号通路增强了椎间盘退变过程中的VEGF表达。
Disc degeneration is a common clinical condition in which damaged discs cause chronic pain; however, a laboratory diagnosis method for its detection is not available. As circulating miRNAs have potential as biomarkers, their application in disc degeneration has not been explored. Here, we prepared serum miRNAs from a mouse disc degeneration model and performed miRNA-Seq and quantitative PCR to characterize disc degeneration-associated miRNAs. We identified three miRNAs, including miR-26a-5p, miR-122-5p and miR-215-5p, undergoing perturbation during the pathogenesis of disc degeneration. Specifically, the levels of miR-26a-5p in the serum demonstrated steady increases in the model of disc degeneration, compared with those in the pre-injury samples of younger age or compared with normal controls of the same age but without disc degeneration, whereas the miRNAs miR-122-5p and miR-215-5p exhibited lower expression in post-injury samples than in their counterparts without the surgery. Moreover, we found that miR-26a-5p targets Smad1 expression, and Smad1 negatively regulates Vegfa expression in disc cells, and thus, miR-26a-5p promotes disc degeneration. In summary, we established a method that consistently profiles circulating miRNAs and identified multiple miRNAs as promising biomarkers for disc degeneration, among which miR-26a-5p enhances VEGF expression during disc degeneration through targeting Smad1 signalling.