Reactive astrocytes are implicated in traumatic spinal cord injury (TSCI). Interestingly, naïve astrocytes can easily transform into neurotoxic reactive astrocytes (A1s) with inflammatory stimulation. Previous studies demonstrated that microRNA(miR)-21a-5p was up-regulated in spinal cord tissue after TSCI; however, it is not clear whether this affected reactive astrocyte polarization. Here, we aim to detect the effects of miR-21a-5p on the induction of A1 formation and the underlying mechanisms. Our study found that the expression of miR-21a-5p was significantly increased while that of Cntfr α was decreased, since naïve astrocytes transformed into A1s 3 days post-TSCI; the binding site between miR-21a-5p and Cntfr α was further confirmed in astrocytes. After treatment with CNTF, the levels of A1 markers decreased while that of A2 increased. The expression of A1 markers significantly decreased with the downregulation of miR-21a-5p, while Cntfr α siRNA treatment caused the opposite both in vitro and in vivo. To summarize, miR-21a-5p/Cntfr α promotes A1 induction and might enhance the inflammatory process of TSCI; furthermore, we identified, for the first time, the effect and potential mechanism by which CNTF inhibits naïve astrocytes transformation into A1s. Collectively, our findings demonstrate that targeting miR-21a-5p represents a prospective therapy for promoting the recovery of TSCI.

中文翻译：

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miR-21a-5p 通过抑制 CNTF/STAT3/Nkrf 通路上调神经毒性反应性星形胶质细胞 (A1) 极化促进创伤性脊髓损伤后的炎症

反应性星形胶质细胞与创伤性脊髓损伤 (TSCI) 有关。有趣的是，幼稚的星形胶质细胞很容易在炎症刺激下转化为具有神经毒性的反应性星形胶质细胞 (A1s)。先前的研究表明，TSCI 后脊髓组织中的 microRNA(miR)-21a-5p 上调；然而，尚不清楚这是否会影响反应性星形胶质细胞极化。在这里，我们旨在检测 miR-21a-5p 对 A1 形成诱导的影响及其潜在机制。我们的研究发现 miR-21a-5p 的表达显着增加，而Cntfr α的表达降低，因为天真的星形胶质细胞在 TSCI 后 3 天转化为 A1s；miR-21a-5p 和Cntfr α之间的结合位点在星形胶质细胞中得到进一步证实。CNTF处理后，A1标志物水平降低，而A2水平升高。随着 miR-21a-5p 的下调，A1 标志物的表达显着降低，而Cntfr α siRNA 处理在体外和体内均导致相反的结果。综上所述，miR-21a-5p/Cntfr α 促进 A1 诱导并可能增强 TSCI 的炎症过程；此外，我们首次确定了 CNTF 抑制幼稚星形胶质细胞转化为 A1 的作用和潜在机制。总的来说，我们的研究结果表明，靶向 miR-21a-5p 代表了一种促进 TSCI 恢复的前瞻性疗法。