Downregulation of LncRNA TUG1 Inhibited TLR4 Signaling Pathway-Mediated Inflammatory Damage After Spinal Cord Ischemia Reperfusion in Rats via Suppressing TRIL Expression
Downregulation of LncRNA TUG1 Inhibited TLR4 Signaling Pathway-Mediated Inflammatory Damage After Spinal Cord Ischemia Reperfusion in Rats via Suppressing TRIL Expression
复制标题
LncRNA TUG1 下调通过抑制 TRIL 表达抑制大鼠脊髓缺血再灌注后 TLR4 信号通路介导的炎症损伤
DOI：
10.1093/jnen/nly126
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发表时间：
2019-03-01
影响因子：
3.2
通讯作者：
Qiang, Ziyun
中科院分区：
文献类型：
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作者：
Jia, Hui;Ma, Hong;Qiang, Ziyun
Toll样受体4(TLR4)和富含亮氨酸重复序列的TLR4相互作用(TRIL)在炎症反应中起着至关重要的作用。本研究探讨了长非编码RNA牛磺酸上调基因1(LncRNA TUG1)在脊髓缺血再灌注损伤中TRIL/TLR4信号转导中的作用。通过鞘内注射siRNAs诱导TUG1和TRIL的表达下调，pcDNA3.3-TRIL诱导TRIL的过度表达。结果表明，缺血再灌注后12h，TUG1mRNA表达水平升高，并伴有TRIL和TLR4介导的NF-κB/IL-1β信号通路表达增加。激活的小胶质细胞，以升高的钙结合受体分子1为标志，加重IR后的后肢神经功能损害和血脊髓屏障(BSCB)渗漏。TUG1基因敲除可抑制促炎症细胞因子TRIL和TLR4信号的表达，抑制小胶质细胞的激活，减轻神经功能缺失和BSCB渗漏。TRIL基因敲除可抑制TLR4介导的炎症反应，而TRIL的表达可逆转TUG1基因敲除所致的炎症抑制效应。提示TUG1基因敲除可通过抑制TRIL的表达，抑制IR后由TLR4介导的NF-κB/IL-1β信号通路的炎性损伤。
Toll-like receptor 4 (TLR4) and TLR4 interactor with leucine-rich repeats (TRIL) play a crucial role in the inflammatory response. This study investigated the role of long noncoding RNA taurine-upregulated gene 1 (lncRNA TUG1) in TRIL/TLR4 signaling in spinal cord ischemia reperfusion (IR) injury. IR injury was induced in experimental rats; knockdown of TUG1 and TRIL was induced by intrathecal injection of siRNAs and overexpression of TRIL was induced by pcDNA3.3-TRIL. The results showed that the mRNA levels of TUG1 were increased at 12 hours after IR; this was accompanied by increased expression of the TRIL- and TLR4-mediated NF-κB/IL-1β signaling pathway. Activated microglia, detected with increased ionized calcium-binding adapter molecule 1 as a marker, exacerbated the hind-limb neurological impairment and blood-spinal cord barrier (BSCB) leakage after IR. TUG1 knockdown inhibited expression of TRIL and TLR4 signaling proinflammatory cytokines and microglial activation, and attenuated neurological deficit and BSCB leakage. TRIL knockdown inhibited the TLR4-mediated inflammatory response, while TRIL expression reversed the inhibited inflammatory effect caused by TUG1 knockdown. These data suggest that TUG1 knockdown inhibited inflammatory damage of the TLR4-mediated NF-κB/IL-1β signaling pathway after IR via suppressing TRIL expression.