MicroRNAs in the Spinal Microglia Serve Critical Roles in Neuropathic Pain

Tang, Simin; Jing, Huan; Song, Fuhu; Huang, Haicheng; Li, Wenjun; Xie, Guiling; Zhou, Jun

doi:10.1007/s12035-020-02102-1

Cited by 21 publications

(13 citation statements)

References 109 publications

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“…At present, many miRNAs have been reported in neurodegenerative diseases (Eyileten et al 2020 ), cancers (Kapoor et al 2020 ; Wilczynski et al 2020 ), bowel disease (Ambrozkiewicz et al 2020 ), and diabetic heart disease (DHD) (Lew et al 2020 ). Although some miRNAs (Kalpachidou et al 2020 ; Tang et al 2020 ) have been reported in NP, reports on how miRNAs and mRNAs jointly regulate the pathogenesis of NP are still limited and have only captured partial insights of the complex pathogenetic mechanisms. In addition, studies have indicated the shift in metabolic processes in NP and nervous system-related diseases, but, to the best of our knowledge, no study has explored the regulatory relationship between miRNAs and metabolic genes, which would be important for understanding the pathogenesis of NP and developing essential metabolic therapies for this condition.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis of the MicroRNA-Metabolic Gene Regulatory Network in Neuropathic Pain and Prediction of Corresponding Potential Therapeutics

et al. 2021

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Neuropathic pain (NP) involves metabolic processes that are regulated by metabolic genes and their non-coding regulator genes such as microRNAs (miRNAs). Here, we aimed at exploring the key miRNA signatures regulating metabolic genes involved in NP pathogenesis. We downloaded NP-related data from public databases and identified differentially expressed microRNAs (miRNAs) and mRNAs through differential gene expression analysis. The miRNA target prediction was performed, and integration with the differentially expressed metabolic genes (DEMGs) was used for constructing the miRNA-DEMG network. Subsequently, functional enrichment analysis and protein–protein interaction (PPI) analysis were performed to explore the role of DEMGs in the regulatory network. The drug prediction was performed based on the DEMGs in the miRNA-DEMG network. A total of 8251 differentially expressed mRNAs (4193 upregulated and 4058 downregulated), and 959 differentially expressed miRNAs (455 upregulated and 504 downregulated) were identified. Moreover, after target gene prediction, a miRNA-DEMG network composed of 22 miRNAs and 113 mRNAs was constructed. The network was constituted of 135 nodes and 236 edges. We found that DEMGs in the network were mainly enriched in metabolic pathways and metabolic processes. A total of 1200 drugs were predicted as potential therapeutics for NP based on the differentially expressed genes, while 170 drugs were predicted for the DEMGs in the miRNA-DEMG network. Conclusively, our study predicted drugs that may be effective against the metabolic changes induced by miRNA dysregulation in NP. This information will help further reveal the pathological mechanism of NP and provide more treatment options for NP patients. Supplementary Information The online version contains supplementary material available at 10.1007/s12031-021-01911-w.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis of the MicroRNA-Metabolic Gene Regulatory Network in Neuropathic Pain and Prediction of Corresponding Potential Therapeutics

et al. 2021

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“…miRNAs are known to play a significant role in NP (Tang, Jing, 2021). Meanwhile, some studies have pointed out that miR-140-3p can regulate RA (Zhong et al, 2020;Zu, Liu, 2021).…”

Section: Propofol Exerts Protective Effect On CCI Rats Via Mir-140-3pmentioning

confidence: 99%

“…MicroRNAs (miRNAs) are regarded as a class of small noncoding RNAs that possess the ability to negatively regulate mRNA levels (Saliminejad et al., 2019). With short ribonucleic acids in the chemical structure, miRNAs have found use in the development of medicines for NP treatment (Tang et al., 2021). Particularly, MicroRNA‐140 was recently highlighted to ameliorate NP and neuroinflammation in CCI rats (J. Li et al., 2020).…”

Section: Introductionmentioning

confidence: 99%

Propofol alleviates neuropathic pain in chronic constriction injury rat models via the microRNA‐140‐3p/Jagged‐1 peptide/Notch signaling pathway

Fang

Yang

Yan

et al. 2021

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Chronic constriction injury (CCI) of the sciatic nerve was used to establish neuropathic pain (NP) models in rats. CCI rats were then treated with propofol (Pro) and their paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured. In addition, the expression patterns of tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and IL‐10 were detected. CCI rats treated with propofol were further injected with antagomiR‐140‐3p to verify the role of miR‐140‐3p in propofol's analgesic actions. In addition to confirming the relationship between miR‐140‐3p and JAG1, the expression patterns of JAG1 itself were detected. Propofol‐treated CCI rats were also injected with Ad‐JAG1 (adenovirus‐packaged JAG1 overexpression vector and Ad‐NC) to test the role of JAG1 in propofol's analgesic mechanism of action. Finally, the levels of JAG1 and Notch pathway‐related proteins were detected Results Propofol was found to alleviate NP, including thermal hyperalgesia and mechanical pain threshold. Propofol could also ameliorate neuroinflammation by up‐regulating the expression of IL‐10 and inhibiting the release of TNF‐α and IL‐1β. Mechanically, propofol enhanced the amount of miR‐140‐3p in CCI rats via the regulation of JAG1. Down‐regulation of miR‐140‐3p, or up‐regulation of JAG1, could reduce the protective effect of propofol against NP. Propofol inhibited the activation of Notch signaling via miR‐140‐3p/JAG1 to realize its analgesic effect Conclusion Our findings indicated that propofol inhibits inflammatory responses and the Notch signaling pathway via miR‐140‐3p/JAG1 to alleviate NP. These data provide evidence to support a potential clinical therapy for NP.

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“…Propofol exerts protective effect on CCI rats via miR-140-3p miRNAs play a signi cant role in neuropathic pain (Tang 2021). Some papers pointed out that miR-140-3p can regulate rheumatoid arthritis (Zhong et al 2020; Zu 2021).…”

Section: Protective Effect Of Propofol On Rats With Npmentioning

confidence: 99%

“…MicroRNAs (miRNAs) are deemed as a class of small noncoding RNAs and could negatively regulate the level of mRNAs (Saliminejad et al 2019). With short ribonucleic acids in chemical structure, miRNAs are utilized to develop medicines for NP treatment (Tang et al 2021). According to the literature, miR-140 was reported to ameliorate NP and neuroin ammation in CCI rats (Li et al 2020b).…”

Section: Introductionmentioning

confidence: 99%

Propofol Alleviates Neuropathic Pain in CCI Rat Model via the miR-140-3p/JAG1/Notch Signaling Pathway

Fang

Yang

Yan

et al. 2021

Preprint

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As a renowned anesthetic, propofol exerts excellent analgesic function in nerve injury. However, the underlying mechanism of propofol on neuropathic pain (NP) remains unknown. The research aims to analyze propofol’s analgesia mechanism to alleviate NP in CCI rats. The chronic constriction injury (CCI) of sciatic nerve was used to established NP rat models. CCI rats were treated with propofol and its paw withdrawal mechanical threshold (PMWT) and paw withdraw thermal latency (PWTL) were measured. The expressions of TNF-α, IL-1β and IL-10 were detected. CCI rats with propofol treatment were injected with antagomiR-140-3p. After the targeting relationship between miR-140-3p and JAG1 was checked, JAG1 expression was detected. Propofol-treated CCI rats were further injected with Ad-JAG1. Finally, the levels of JAG1 and Notch pathway-related proteins were detected. As a result, propofol could alleviate NP, including thermal hyperalgesia and mechanical pain threshold, and ameliorate neuroinflammation. Mechanically, propofol enhanced the level of miR-140-3p in CCI rats. JAG1 was a direct target of miR-140-3p. The downregulation of miR-140-3p or upregulation of JAG1 could reduce the protective effect of propofol against NP. Propofol inhibited activation of Notch signaling via miR-140-3p/JAG1. Overall, Propofol could inhibit the neuroinflammation and Notch signaling pathway via miR-140-3p/JAG1 to alleviate NP.

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MicroRNAs in the Spinal Microglia Serve Critical Roles in Neuropathic Pain

Cited by 21 publications

References 109 publications

Bioinformatics Analysis of the MicroRNA-Metabolic Gene Regulatory Network in Neuropathic Pain and Prediction of Corresponding Potential Therapeutics

Bioinformatics Analysis of the MicroRNA-Metabolic Gene Regulatory Network in Neuropathic Pain and Prediction of Corresponding Potential Therapeutics

Propofol alleviates neuropathic pain in chronic constriction injury rat models via the microRNA‐140‐3p/Jagged‐1 peptide/Notch signaling pathway

Propofol Alleviates Neuropathic Pain in CCI Rat Model via the miR-140-3p/JAG1/Notch Signaling Pathway

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