miR-124a and miR-155 enhance differentiation of regulatory T cells in patients with neuropathic pain

Heyn, Jens; Luchting, Benjamin; Hinske, Ludwig Christian; Hübner, Max; Azad, Shahnaz Christina; Kreth, Simone

doi:10.1186/s12974-016-0712-6

Cited by 68 publications

(59 citation statements)

References 36 publications

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“…Indeed, miRNAs had been frequently reported as a therapeutic potential target of NP in the past few years (Andersen et al, 2014; Heyn et al, 2016). Recent studies have also shown that peripheral noxious stimuli induced changes in the expression of lncRNAs, which are associated with pain hypersensitivity underlying NP (Zhao et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Identification of the Spinal Expression Profile of Non-coding RNAs Involved in Neuropathic Pain Following Spared Nerve Injury by Sequence Analysis

Zhou

Xiong

Chen

et al. 2017

Front. Mol. Neurosci.

132

134

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Neuropathic pain (NP) is caused by damage to the nervous system, resulting in aberrant pain, which is associated with gene expression changes in the sensory pathway. However, the molecular mechanisms are not fully understood. A non-coding Ribose Nucleic Acid (ncRNA) is an RNA molecule that is not translated into a protein. NcRNAs are involved in many cellular processes, and mutations or imbalances of the repertoire within the body can cause a variety of diseases. Although ncRNAs have recently been shown to play a role in NP pathogenesis, the specific effects of ncRNAs in NP remain largely unknown. In this study, sequencing analysis was performed to investigated the expression patterns of ncRNAs in the spinal cord following spared nerve injury-induced NP. A total of 134 long non-coding RNAs (lncRNAs), 12 microRNAs (miRNAs), 188 circular RNAs (circRNAs) and 1066 mRNAs were significantly regulated at 14 days after spared nerve injury (SNI) surgery. Next, quantitative real-time polymerase chain reaction (PCR) was performed to validate the expression of selected lncRNAs, miRNAs, circRNAs, and mRNAs. Bioinformatics tools and databases were employed to explore the potential ncRNA functions and relationships. Our data showed that the most significantly involved pathways in SNI pathogenesis were ribosome, PI3K-Akt signaling pathway, focal adhesion, ECM-receptor interaction, amoebiasis and protein digestion and absorption. In addition, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA network of NP was constructed. This is the first study to comprehensively identify regulated ncRNAs of the spinal cord and to demonstrate the involvement of different ncRNA expression patterns in the spinal cord of NP pathogenesis by sequence analysis. This information will enable further research on the pathogenesis of NP and facilitate the development of novel NP therapeutics targeting ncRNAs.

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Section: Discussionmentioning

confidence: 99%

Identification of the Spinal Expression Profile of Non-coding RNAs Involved in Neuropathic Pain Following Spared Nerve Injury by Sequence Analysis

Zhou

Xiong

Chen

et al. 2017

Front. Mol. Neurosci.

132

134

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show abstract

“…Accordingly, the cytokine profile revealed increased levels of FoxP3 and TGF‐β mRNA expression in peripheral blood mononuclear cells (Luchting et al, ; Luchting et al, ). A similar increase in circulating Treg cells has been observed in a range of clinical neuropathic pain conditions and has been speculated to represent an endogenous attempt to limit inflammation and subsequently reduce pain levels in affected patients (Heyn et al, ).…”

Section: Treg Cells In Neuropathic Painmentioning

confidence: 58%

The role of regulatory T cells in nervous system pathologies

Duffy

Keating

Perera

et al. 2017

J of Neuroscience Research

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Regulatory T (Treg) cells are a special subpopulation of immunosuppressive T cells that are essential for sustaining immune homeostasis. They maintain self-tolerance, inhibit autoimmunity, and act as critical negative regulators of inflammation in various pathological states including autoimmunity, injury, and degeneration of the nervous system. Treg cells are known to convey both beneficial and detrimental influences in certain disease contexts, and accumulating research suggests that their action may be altered in a range of peripheral and central nervous system pathologies. In this review, we discuss emerging evidence for the dichotomous role of Treg cells in various neurological pathologies including multiple sclerosis, Guillain-Barré syndrome, neuropathic pain, traumatic central nervous system injury, stroke, and neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease. We are in the early stages of uncovering the role of Treg cells in these conditions, and a better understanding of the ways in which these cells operate in the nervous system will enable us to develop novel therapeutic interventions.

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“…We chose these miRNAs because the level of those miRNAs had been found disturbed in neuropathic pain models or patients, and related to the pathogenesis of nervous system disorder. 7,9,18,19 We found the level of miR-132 was upregulated and miR-101 was downregulated when compared with healthy control (Figure 1). To understand whether the alteration of plasma miRNA level was consistent with the local tissues underwent neuropathic pain, we extracted RNAs from sural nerve biopsies, and detected the miR-132 and miR-101 level.…”

Section: Resultsmentioning

confidence: 87%

“…Total RNA was extracted from plasma and the expression of six candidate miRNAs, including miR‐132, miR‐96, miR‐146a, miR‐101, miR‐124, and miR‐155 was quantified by quantitative RT‐PCR. We chose these miRNAs because the level of those miRNAs had been found disturbed in neuropathic pain models or patients, and related to the pathogenesis of nervous system disorder . We found the level of miR‐132 was upregulated and miR‐101 was downregulated when compared with healthy control (Figure ).…”

Section: Resultsmentioning

confidence: 99%

MiR‐101 relates to chronic peripheral neuropathic pain through targeting KPNB1 and regulating NF‐κB signaling

Liu

Xue

Wang

et al. 2019

The Kaohsiung J of Med Scie

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Accumulating evidences indicates that chronic neuropathic pain is a kind of neuro‐immune disorder with enhanced activation of the immune system. Although the prevalence is very high, neuropathic pain remains extremely difficult to cure. miRNAs are a group of short nonprotein coding RNAs, regulating target genes expression via targeting 3′‐untranslated region. More and more research indicates that altered miRNAs expression profile relates to the pathogenesis of neuropathic pain. In this study, we firstly detected the expression of six candidate miRNAs in the plasma samples from 23 patients with neuropathic pain and 10 healthy controls. Subsequently, the level of miR‐132 and miR‐101 was detected in the sural nerve biopsies. We found miR‐101 level was significantly repressed in both the plasma samples and sural nerve biopsies from neuropathic pain patients. Predicted by bioinformatics tools and confirmed by dual luciferase assay and immunoblotting, we identified that KPNB1 is a direct target of miR‐101. The negative correlation between miR‐101 and KPNB1 was also confirmed in the sural nerve biopsies, and miR‐101 reduction relates to the activation of NF‐κB signaling in vivo and in vitro which contributes to the pathogenesis of neuropathic pain.

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miR-124a and miR-155 enhance differentiation of regulatory T cells in patients with neuropathic pain

Cited by 68 publications

References 36 publications

Identification of the Spinal Expression Profile of Non-coding RNAs Involved in Neuropathic Pain Following Spared Nerve Injury by Sequence Analysis

Identification of the Spinal Expression Profile of Non-coding RNAs Involved in Neuropathic Pain Following Spared Nerve Injury by Sequence Analysis

The role of regulatory T cells in nervous system pathologies

MiR‐101 relates to chronic peripheral neuropathic pain through targeting KPNB1 and regulating NF‐κB signaling

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