Lyn-mediated glycolysis enhancement of microglia contributes to neuropathic pain through facilitating IRF5 nuclear translocation in spinal dorsal horn.
Lyn-mediated glycolysis enhancement of microglia contributes to neuropathic pain through facilitating IRF5 nuclear translocation in spinal dorsal horn.
复制标题
DOI：
10.1111/jcmm.17759
复制
发表时间：
2023-06
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
作者：
小胶质细胞的促炎表型通常诱导神经病理性疼痛中的神经炎症反应。糖代谢转变为糖酵解可以促进小胶质细胞的促炎表型转变。组学数据分析表明林恩失调在神经性疼痛中起关键作用。本研究旨在探讨林恩介导的小胶质细胞糖酵解促进神经病理性疼痛的机制。采用慢性压迫性损伤（CCI）建立神经病理性疼痛模型，测定痛阈和林恩蛋白表达。鞘内给予林恩抑制剂Bafetinib和siRNA‐lyn敲低，以评价林恩对体内和体外小胶质细胞痛阈、糖酵解和干扰素调节因子5（IRF 5）核转位的影响。利用ChIP技术观察转录因子SP1、PU.1与糖酵解基因启动子的结合情况。最后，评价了糖酵解与小胶质细胞的促炎表型转变之间的关系。CCI导致脊髓背角小胶质细胞林恩表达上调，糖酵解增强。在CCI小鼠中，Bafetinib或siRNA‐林恩鞘内敲低可减轻疼痛痛觉过敏，抑制糖酵解增强并抑制IRF 5的核转位。此外，IRF5促进转录因子SP1，PU.1与糖酵解基因启动子的结合，然后增强的糖酵解促进小胶质细胞的增殖和促炎表型转变，并促成神经病理性疼痛。林恩介导的小胶质细胞糖酵解增强通过促进脊髓背角中的IRF 5核转位而促成神经病理性疼痛。
The pro‐inflammatory phenotype of microglia usually induces neuroinflammatory reactions in neuropathic pain. Glycometabolism shift to glycolysis can promote the pro‐inflammatory phenotype transition of microglia. The omics data analysis suggest a critical role for Lyn dysregulation in neuropathic pain. The present study aimed at exploring the mechanism of Lyn‐mediated glycolysis enhancement of microglia in neuropathic pain. Neuropathic pain model was established by chronic constriction injury (CCI), then pain thresholds and Lyn expression were measured. Lyn inhibitor Bafetinib and siRNA‐lyn knockdown were administrated intrathecally to evaluate the effects of Lyn on pain thresholds, glycolysis and interferon regulatory factor 5 (IRF5) nuclear translocation of microglia in vivo and in vitro. ChIP was carried out to observe the binding of transcription factors SP1, PU.1 to glycolytic gene promoters by IRF5 knockdown. Finally, the relationship between glycolysis and pro‐inflammatory phenotype transition of microglia was evaluated. CCI led to the upregulation of Lyn expression and glycolysis enhancement in microglia of spinal dorsal horn. Bafetinib or siRNA‐lyn knockdown intrathecally alleviated pain hyperalgesia, suppressed glycolysis enhancement and inhibited nuclear translocation of IRF5 in CCI mice. Also, IRF5 promoted the binding of transcription factors SP1, PU.1 to glycolytic gene promoters, and then the enhanced glycolysis facilitated the proliferation and pro‐inflammatory phenotype transition of microglia and contributed to neuropathic pain. Lyn‐mediated glycolysis enhancement of microglia contributes to neuropathic pain through facilitating IRF5 nuclear translocation in spinal dorsal horn.
登录
查看更多内容
影响因子：
20.3
作者：
Federzoni, Elena A.;Valk, Peter J. M.;Tschan, Mario P.
通讯作者：
Tschan, Mario P.
DOI：
10.1073/pnas.1418399111
发表时间：
2014-12-09
影响因子：
11.1
作者：
Lopez-Pelaez, Marta;Lamont, Douglas J.;Cohen, Philip
通讯作者：
Cohen, Philip
DOI：
10.1126/science.1250684
发表时间：
2014-09-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cheng SC;Quintin J;Cramer RA;Shepardson KM;Saeed S;Kumar V;Giamarellos-Bourboulis EJ;Martens JH;Rao NA;Aghajanirefah A;Manjeri GR;Li Y;Ifrim DC;Arts RJ;van der Veer BM;Deen PM;Logie C;O'Neill LA;Willems P;van de Veerdonk FL;van der Meer JW;Ng A;Joosten LA;Wijmenga C;Stunnenberg HG;Xavier RJ;Netea MG
通讯作者：
Netea MG
影响因子：
12.4
作者：
Amo-Aparicio J;Garcia-Garcia J;Francos-Quijorna I;Urpi A;Esteve-Codina A;Gut M;Quintana A;Lopez-Vales R
通讯作者：
Lopez-Vales R
影响因子：
7.3
作者：
Franks SE;Cambier JC
通讯作者：
Cambier JC