C/EBPβ Participates in Nerve Trauma-Induced TLR7 Upregulation in Primary Sensory Neurons

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2022 Feb 10

PMID 35141864

Authors

Long He

Jing Cao

Bao-Chun Jiang

Jian-Jun Yang

Yuan-Xiang Tao

Yanqiu Ai

Affiliations

Soon will be listed here.

Abstract

Nerve trauma-induced toll-like receptor 7 (TLR7) expression level increases in primary sensory neurons in injured dorsal root ganglion (DRG) avails to neuropathic pain, but the reason is still unknown. In the current study, we showed that unilateral lumbar 4 (L4) spinal nerve ligation (SNL) upregulated CCAAT/enhancer-binding protein-β (C/EBPβ) expression in ipsilateral L4 DRG. Preventing this elevation attenuated the SNL-induced upregulation of TLR7 in the ipsilateral L4 DRG and inhibited cold/thermal hyperalgesia and mechanical allodynia. In injected DRG, mimicking nerve trauma-induced C/EBPβ upregulation increased TLR7 levels, augmented responses to cold/thermal/mechanical stimuli, and caused ipsilateral spontaneous pain with no SNL. Mechanistically, SNL upregulated binding of increased C/EBPβ to Tlr7 promoter in ipsilateral L4 DRG. Accorded that C/EBPβ could trigger the activation of Tlr7 promoter and co-expressed with Tlr7 mRNA in individual DRG neurons, our findings strongly suggest the role of C/EBPβ in nerve trauma-mediated TLR7 upregulation in injured primary sensory neurons.

Citing Articles

Multilevel analysis of the central-peripheral-target organ pathway: contributing to recovery after peripheral nerve injury.

Song X, Li R, Chu X, Li Q, Li R, Li Q Neural Regen Res. 2024; 20(10):2807-2822.

PMID: 39435615 PMC: 11826472. DOI: 10.4103/NRR.NRR-D-24-00641.

Rbfox1 regulates alternative splicing of Nrcam in primary sensory neurons to mediate peripheral nerve injury-induced neuropathic pain.

He L, Guo H, Wang H, Zhu K, Li D, Zhang C Neurotherapeutics. 2024; 21(1):e00309.

PMID: 38241164 PMC: 10903086. DOI: 10.1016/j.neurot.2023.e00309.

References

Mao Q, Wu S, Gu X, Du S, Mo K, Sun L . DNMT3a-triggered downregulation of K 1.1 gene in primary sensory neurons contributes to paclitaxel-induced neuropathic pain. Int J Cancer. 2019; 145(8):2122-2134. PMC: 6660426. DOI: 10.1002/ijc.32155. View

Yuan J, Wen J, Wu S, Mao Y, Mo K, Li Z . Contribution of dorsal root ganglion octamer transcription factor 1 to neuropathic pain after peripheral nerve injury. Pain. 2018; 160(2):375-384. PMC: 6344274. DOI: 10.1097/j.pain.0000000000001405. View

Liang L, Gu X, Zhao J, Wu S, Miao X, Xiao J . G9a participates in nerve injury-induced Kcna2 downregulation in primary sensory neurons. Sci Rep. 2016; 6:37704. PMC: 5118693. DOI: 10.1038/srep37704. View

Mo K, Wu S, Gu X, Xiong M, Cai W, Atianjoh F . MBD1 Contributes to the Genesis of Acute Pain and Neuropathic Pain by Epigenetic Silencing of and Genes in Primary Sensory Neurons. J Neurosci. 2018; 38(46):9883-9899. PMC: 6234297. DOI: 10.1523/JNEUROSCI.0880-18.2018. View

Hoshikawa N, Sakai A, Takai S, Suzuki H . Targeting Extracellular miR-21-TLR7 Signaling Provides Long-Lasting Analgesia in Osteoarthritis. Mol Ther Nucleic Acids. 2019; 19:199-207. PMC: 6920297. DOI: 10.1016/j.omtn.2019.11.011. View

Akira S, Uematsu S, Takeuchi O . Pathogen recognition and innate immunity. Cell. 2006; 124(4):783-801. DOI: 10.1016/j.cell.2006.02.015. View

Huang T, Fu G, Gao J, Zhang Y, Cai W, Wu S . Fgr contributes to hemorrhage-induced thalamic pain by activating NF-κB/ERK1/2 pathways. JCI Insight. 2020; 5(20). PMC: 7605540. DOI: 10.1172/jci.insight.139987. View

Yi H, Liu S, Kashiwagi Y, Ikegami D, Huang W, Kanda H . Phosphorylated CCAAT/Enhancer Binding Protein β Contributes to Rat HIV-Related Neuropathic Pain: and Studies. J Neurosci. 2017; 38(3):555-574. PMC: 5777110. DOI: 10.1523/JNEUROSCI.3647-16.2017. View

Liang L, Zhao J, Gu X, Wu S, Mo K, Xiong M . G9a inhibits CREB-triggered expression of mu opioid receptor in primary sensory neurons following peripheral nerve injury. Mol Pain. 2016; 12. PMC: 5153028. DOI: 10.1177/1744806916682242. View

10.

Lutz B, Bekker A, Tao Y . Noncoding RNAs: new players in chronic pain. Anesthesiology. 2014; 121(2):409-17. PMC: 4110167. DOI: 10.1097/ALN.0000000000000265. View

11.

Kim S, Chung J . An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain. 1992; 50(3):355-363. DOI: 10.1016/0304-3959(92)90041-9. View

12.

Li Z, Mao Y, Liang L, Wu S, Yuan J, Mo K . The transcription factor C/EBPβ in the dorsal root ganglion contributes to peripheral nerve trauma-induced nociceptive hypersensitivity. Sci Signal. 2017; 10(487). PMC: 5665022. DOI: 10.1126/scisignal.aam5345. View

13.

Chung J, Chung K . Importance of hyperexcitability of DRG neurons in neuropathic pain. Pain Pract. 2006; 2(2):87-97. DOI: 10.1046/j.1533-2500.2002.02011.x. View

14.

Zhao J, Liang L, Gu X, Li Z, Wu S, Sun L . DNA methyltransferase DNMT3a contributes to neuropathic pain by repressing Kcna2 in primary afferent neurons. Nat Commun. 2017; 8:14712. PMC: 5344974. DOI: 10.1038/ncomms14712. View

15.

Wen J, Yang Y, Wu S, Wei G, Jia S, Hannaford S . Long noncoding RNA H19 in the injured dorsal root ganglion contributes to peripheral nerve injury-induced pain hypersensitivity. Transl Perioper Pain Med. 2020; 7(2):176-184. PMC: 7041488. View

16.

Costigan M, Scholz J, Woolf C . Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci. 2009; 32:1-32. PMC: 2768555. DOI: 10.1146/annurev.neuro.051508.135531. View

17.

Campbell J, Meyer R . Mechanisms of neuropathic pain. Neuron. 2006; 52(1):77-92. PMC: 1810425. DOI: 10.1016/j.neuron.2006.09.021. View

18.

Sun L, Gu X, Pan Z, Guo X, Liu J, Atianjoh F . Contribution of DNMT1 to Neuropathic Pain Genesis Partially through Epigenetically Repressing in Primary Afferent Neurons. J Neurosci. 2019; 39(33):6595-6607. PMC: 6697395. DOI: 10.1523/JNEUROSCI.0695-19.2019. View

19.

He L, Han G, Wu S, Du S, Zhang Y, Liu W . Toll-like receptor 7 contributes to neuropathic pain by activating NF-κB in primary sensory neurons. Brain Behav Immun. 2020; 87:840-851. PMC: 7316623. DOI: 10.1016/j.bbi.2020.03.019. View

20.

Liu T, Xu Z, Park C, Berta T, Ji R . Toll-like receptor 7 mediates pruritus. Nat Neurosci. 2010; 13(12):1460-2. PMC: 2991508. DOI: 10.1038/nn.2683. View