Hypoxia inducible factor-1 (HIF-1α) reduced inflammation in spinal cord injury via miR-380-3p/ NLRP3 by Circ 0001723
Hypoxia inducible factor-1 (HIF-1α) reduced inflammation in spinal cord injury via miR-380-3p/ NLRP3 by Circ 0001723
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DOI：
10.1186/s40659-020-00302-6
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发表时间：
2020-01-01
影响因子：
6.7
通讯作者：
Wu, Junsong
中科院分区：
文献类型：
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作者：
Li, Xigong;Lou, Xianfeng;Wu, Junsong
背景：脊髓损伤是一种严重的中枢神经系统损伤。本研究旨在评价HIF-1 α对脊髓损伤（SCI）炎症的影响，揭示其抗炎症的分子机制。结果：脊髓损伤模型大鼠HIF-1 α降低，HIF-1 α活化降低脊髓损伤模型大鼠tnf - α、IL-1 β、IL-6、IL-18水平。同时，SCI模型大鼠中Circ 0001723表达下调，miR-380-3p表达上调。体外模型与对照组相比，Circ 0001723下调可提高tnf - α、IL-1 β、IL-6和IL-18水平。然而，过表达Circ 0001723可降低体外模型中tnf - α、IL-1 β、IL-6和IL-18的水平。在体外模型中，Circ 0001723下调miR-380-3p抑制HIF-1 α蛋白表达，诱导NLRP3和Caspase-1蛋白表达。然后，在体外模型中，HIF-1 α的失活降低了Circ 0001723的促炎症作用。si-NLRP3还通过促进细胞自噬抑制Circ 0001723体外模型的促炎作用。结论：我们得出HIF-1 α通过Circ 0001723通过miR-380-3p/ NLRP3减少脊髓损伤中的炎症。
Background: Spinal cord injury (SCI) is a severe central nervous system trauma. The present study aimed to evaluate the effect of HIF-1 alpha on inflammation in spinal cord injury (SCI) to uncover the molecular mechanisms of anti-inflammation.Results: HIF-1 alpha was reduced in SCI model rats and HIF-1 alpha activation reduced TNF-alpha, IL-1 beta, IL-6 and IL-18 levels in SCI model rats. Meanwhile, Circ 0001723 expression was down-regulated and miR-380-3p expression was up-regulated in SCI model rats. In vitro model, down-regulation of Circ 0001723 promoted TNF-alpha, IL-1 beta, IL-6 and IL-18 levels, compared with control negative group. However, over-expression of Circ 0001723 reduced TNF-alpha, IL-1 beta, IL-6 and IL-18 levels in vitro model. Down-regulation of Circ 0001723 suppressed HIF-1 alpha protein expressions and induced NLRP3 and Caspase-1 protein expressions in vitro model by up-regulation of miR-380-3p. Next, inactivation of HIF-1 alpha reduced the pro-inflammation effects of Circ 0001723 in vitro model. Then, si-NLRP3 also inhibited the pro-inflammation effects of Circ 0001723 in vitro model via promotion of autophagy.Conclusions: We concluded that HIF-1 alpha reduced inflammation in spinal cord injury via miR-380-3p/ NLRP3 by Circ 0001723.