CCR1 enhances SUMOylation of DGCR8 by up-regulating ERK phosphorylation to promote spinal nerve ligation-induced neuropathic pain

Shi, Cunxian; Jin, Jin; Xu, Hongyu; Ma, Jiahai; Li, Tao; Xie, Yonggang; Li, Zhen

doi:10.1038/s41434-021-00285-3

Cited by 8 publications

(7 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has also been reported that cc-chemokine ligand 4 (CCL4) is involved in the induction of neuropathic pain after peripheral nerve injury, confirming our results that CCL4 is one of the hub genes. CCR1 was reported to enhance modification of DGCR8 by SUMO1 through phosphorylation of ERK, thereby promoting activation of spinal microglia and inflammatory responses and increasing pain sensitivity in SNL rats (Shi et al, 2022). Our research provides additional potential therapeutic targets for neuropathic pain.…”

Section: A B Figurementioning

confidence: 62%

Functional investigation and two-sample Mendelian randomization study of neuropathic pain hub genes obtained by WGCNA analysis

et al. 2023

View full text Add to dashboard Cite

ObjectiveNeuropathic pain as a complex chronic disease that occurs after neurological injury, however the underlying mechanisms are not clarified in detail, hence therapeutic options are limited. The purpose of this study was to explore potential hub genes for neuropathic pain and evaluate the clinical application of these genes in predicting neuropathic pain.MethodsDifferentially expressed analysis and weighted gene co-expression network analysis (WGCNA) was used to explore new neuropathic pain susceptibility modules and hub genes. KEGG and GO analyses was utilized to explore the potential role of these hub genes. Nomogram model and ROC curves was established to evaluate the diagnostic efficacy of hub genes. Additionally, the correlation of IL-2 with immune infiltration was explored. Finally, a Mendelian randomization study was conducted to determine the causal effect of IL-2 on neuropathic pain based on genome-wide association studies.ResultsWGCNA was performed to establish the networks of gene co-expression, screen for the most relevant module, and screen for 440 overlapping WGCNA-derived key genes. GO and KEGG pathway enrichment analyses demonstrated that the key genes were correlated with cytokine receptor binding, chemokine receptor binding, positive regulation of JAK–STAT cascade, chemokine-mediated signaling pathway, PI3K-AKT pathway and chemokine pathway. Through Cytoscape software, top ten up-regulated genes with high scores were IL2, SMELL, CCL4, CCR3, CXCL1, CCR1, HGF, CXCL2, GATA3, and CRP. In addition, nomogram model performed well in predicting neuropathic pain risk, and with the ROC curve, the model was showed to be effective in diagnosis. Finally, IL2 was selected and we observed that IL2 was causally associated with immune cell infiltrates in trigeminal neuralgia. In inverse variance weighting, we found that IL2 was associated with the risk of trigeminal neuralgia with an OR of 1.203 (95% CI = 1.004–1.443, p = 0.045).ConclusionWe constructed a WGCNA-based co-expression network and identified neuropathic pain-related hub genes, which may offer further insight into pre-symptomatic diagnostic approaches and may be useful for the study of molecular mechanisms for understanding neuropathic pain risk genes.

show abstract

Section: A B Figurementioning

confidence: 62%

Functional investigation and two-sample Mendelian randomization study of neuropathic pain hub genes obtained by WGCNA analysis

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Moreover, CCR1 contributes to inflammatory processes in Alzheimer's disease [121] and autoimmune encephalomyelitis [122]. Furthermore, the importance of CCR1 was confirmed in SNL [123] and CCI [65,66] mouse/rat models of neuropathic pain. The published data support the hypothesis that pharmacological modulation of CCR1 may represent a new strategy for effective treatment of PNS and CNS injury-however, further research, especially clinical studies, is still necessary.…”

Section: Ccr1-ligands and Pharmacological Modulationmentioning

confidence: 89%

CC Chemokine Family Members’ Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury—A Review of Clinical and Experimental Findings

Ciechanowska,

Mika

2024

IJMS

View full text Add to dashboard Cite

Despite significant progress in modern medicine and pharmacology, damage to the nervous system with various etiologies still poses a challenge to doctors and scientists. Injuries lead to neuroimmunological changes in the central nervous system (CNS), which may result in both secondary damage and the development of tactile and thermal hypersensitivity. In our review, based on the analysis of many experimental and clinical studies, we indicate that the mechanisms occurring both at the level of the brain after direct damage and at the level of the spinal cord after peripheral nerve damage have a common immunological basis. This suggests that there are opportunities for similar pharmacological therapeutic interventions in the damage of various etiologies. Experimental data indicate that after CNS/PNS damage, the levels of 16 among the 28 CC-family chemokines, i.e., CCL1, CCL2, CCL3, CCL4, CCL5, CCL6, CCL7, CCL8, CCL9, CCL11, CCL12, CCL17, CCL19, CCL20, CCL21, and CCL22, increase in the brain and/or spinal cord and have strong proinflammatory and/or pronociceptive effects. According to the available literature data, further investigation is still needed for understanding the role of the remaining chemokines, especially six of them which were found in humans but not in mice/rats, i.e., CCL13, CCL14, CCL15, CCL16, CCL18, and CCL23. Over the past several years, the results of studies in which available pharmacological tools were used indicated that blocking individual receptors, e.g., CCR1 (J113863 and BX513), CCR2 (RS504393, CCX872, INCB3344, and AZ889), CCR3 (SB328437), CCR4 (C021 and AZD-2098), and CCR5 (maraviroc, AZD-5672, and TAK-220), has beneficial effects after damage to both the CNS and PNS. Recently, experimental data have proved that blockades exerted by double antagonists CCR1/3 (UCB 35625) and CCR2/5 (cenicriviroc) have very good anti-inflammatory and antinociceptive effects. In addition, both single (J113863, RS504393, SB328437, C021, and maraviroc) and dual (cenicriviroc) chemokine receptor antagonists enhanced the analgesic effect of opioid drugs. This review will display the evidence that a multidirectional strategy based on the modulation of neuronal–glial–immune interactions can significantly improve the health of patients after CNS and PNS damage by changing the activity of chemokines belonging to the CC family. Moreover, in the case of pain, the combined administration of such antagonists with opioid drugs could reduce therapeutic doses and minimize the risk of complications.

show abstract

“…Besides, mature mDCs increase their expression of CCR7 to migrate towards chemokines constitutively expressed in the secondary lymphoid organs [30]. Immature mDCs express CCR1, CCR2 and CCR5; the ligands for these receptors are produced at sites of in ammation and act as chemoattractant for DCs [31][32][33]. In addition, the production of IL-12 and IL-10 by mDCs are the vital elements in balancing the in ammation responses.…”

Section: Discussionmentioning

confidence: 99%

TIPE2 protein negatively mediates restoration of myeloid dendritic cells in patients with chronic hepatitis B

Ma,

Kang,

Wei

et al. 2023

Preprint

View full text Add to dashboard Cite

Background Hepatitis B virus (HBV) causes persistence in a subgroup of patients and impaired myeloid dendritic cells (mDCs) functions have been observed in these patients, and the effect could be remedied by treatment with interferon-α (IFN-α)-based antiviral therapies. However, the biological functions of mDCs in HBV infection remains largely unexplored. Methods TIPE2 expression in mDCs was analyzed by qRT-PCR, western blot and flow cytometry. The release of cytokines was assessed using enzyme-linked immunosorbent assay (ELISA). Downregulation of TIPE2 expression was constructed via siRNA. Results Our results showed that TIPE2 was significantly increased in mDCs isolated from chronically HBV-infected subjects compared with healthy subjects or patients achieving antiviral treatment of sustained virological responses (SVR). Interestingly, IFN-α treatment could decrease the expression of TIPE2 in mDCs from HBV patients than that untreated patients, SVR patients, or healthy subjects. Moreover, TIPE2 expression in mDCs was decreased in healthy subjects but not HBV patients after stimulating with poly I:C, while the difference could be abrogated by the treatment with IFN-α in vitro. In addition, TIPE2 expression by poly I:C activated mDCs, with or without IFN-α treatment, negatively correlated with the expression of CD86 and CCR7, and the secretion of interleukin-12 (IL-12), but positively associated with the production of IL-10. Finally, downregulation expression of TIPE2 could increase the production of IL-12 and decrease IL-10 secretion in mDCs of chronically HBV-infected individuals. Conclusions Our study suggested that TIPE2 was a crucial factor in negatively mediating innate immune responses during chronic viral infection.

show abstract

CCR1 enhances SUMOylation of DGCR8 by up-regulating ERK phosphorylation to promote spinal nerve ligation-induced neuropathic pain

Cited by 8 publications

References 30 publications

Functional investigation and two-sample Mendelian randomization study of neuropathic pain hub genes obtained by WGCNA analysis

Functional investigation and two-sample Mendelian randomization study of neuropathic pain hub genes obtained by WGCNA analysis

CC Chemokine Family Members’ Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury—A Review of Clinical and Experimental Findings

TIPE2 protein negatively mediates restoration of myeloid dendritic cells in patients with chronic hepatitis B

Contact Info

Product

Resources

About