TLR4 promotes microglial pyroptosis via lncRNA-F630028O10Rik by activating PI3K/AKT pathway after spinal cord injury
TLR4 promotes microglial pyroptosis via lncRNA-F630028O10Rik by activating PI3K/AKT pathway after spinal cord injury
复制标题
脊髓损伤后TLR4通过lncRNAF630028O10Rik激活PI3K/AKT通路促进小胶质细胞焦亡
DOI：
10.1038/s41419-020-02824-z
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发表时间：
2020-08-10
影响因子：
9
通讯作者：
Lyu, Feizhou
中科院分区：
文献类型：
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作者：
Xu, Shun;Wang, Jin;Lyu, Feizhou
神经炎症在脊髓损伤（SCI）的继发性阶段起着至关重要的作用，并且在Toll样受体4（TLR 4）激活后启动。然而，下游机制仍然未知。焦亡是一种炎症性程序性细胞死亡，与神经炎症密切相关，最近的研究表明，它可以通过TLR 4来调节。此外，一些研究表明，基于长链非编码RNA（lncRNA）的机制与炎症调节中TLR 4下游的信号转导有关。因此，在这项研究中，我们想确定TLR 4是否可以通过lncRNA调节SCI后的焦亡。我们的结果表明，TLR 4在SCI后被激活，并促进lncRNA-F630028 O 10 Rik的表达。这种lncRNA作为miR-1231- 5 p/Col 1a 1轴的ceRNA发挥作用，并通过激活PI 3 K/AKT通路增强SCI后小胶质细胞的焦凋亡。此外，我们确定STAT 1是IncRNA-F630028 O 10 Rik的上游转录因子，并由损伤响应性TLR 4/MyD 88信号诱导。我们的发现为治疗SCI提供了新的见解和新的治疗策略。
Neuroinflammation plays a crucial role in the secondary phase of spinal cord injury (SCI), and is initiated following the activation of toll-like receptor 4 (TLR4). However, the downstream mechanism remains unknown. Pyroptosis is a form of inflammatory programmed cell death, which is closely involved in neuroinflammation, and it can be regulated by TLR4 according to a recent research. In addition, several studies have shown that long non-coding RNAs (lncRNAs) based mechanisms were related to signal transduction downstream of TLR4 in the regulation of inflammation. Thus, in this study, we want to determine whether TLR4 can regulate pyroptosis after SCI via lncRNAs. Our results showed that TLR4 was activated following SCI and promoted the expression of lncRNA-F630028O10Rik. This lncRNA functioned as a ceRNA for miR-1231-5p/Col1a1 axis and enhanced microglial pyroptosis after SCI by activating the PI3K/AKT pathway. Furthermore, we determined STAT1 was the upstream transcriptional factor of IncRNA-F630028O10Rik and was induced by the damage-responsive TLR4/MyD88 signal. Our findings provide new insights and a novel therapeutic strategy for treating SCI.