MicroRNA-7, synergizes with RORα, negatively controls the pathology of brain tissue inflammation

Yue, Dongxu; Zhao, Juanjuan; Chen, Huizi; Guo, Ming; Chen, Chao; Zhou, Yue; Xu, Lin

doi:10.1186/s12974-020-1710-2

Cited by 18 publications

(27 citation statements)

References 71 publications

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“…We found several POU family transcription factors(56) (POU2F3, POU2F2, and BRN1), which have critical roles in inflammation (57)(58)(59) and neurodevelopment (60)(61)(62). Moreover, we identified the nuclear orphan receptor, RORα, which is also important in neuroinflammation (63)(64)(65) (Figure 2h). While the DLPFC and NAc vary in how each coordinate their respective signaling pathways, nevertheless, our data demonstrate that both regions share common neuroinflammation and ECM pathways, suggesting the importance of both in alterations related to chronic opioids.…”

Section: Enrichment Of Differentially Expressed Transcripts Involved mentioning

confidence: 91%

Transcriptional alterations in opioid use disorder reveal an interplay between neuroinflammation and synaptic remodeling

Seney

Moon-Kim

Glausier

et al. 2020

Preprint

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Prevalence rates of opioid use disorder (OUD) have increased dramatically, accompanied by a surge of overdose deaths. While opioid dependence has been extensively studied in preclinical models, we still have a very limited understanding of the biological changes that occur in the brains of people who chronically use opioids and who are diagnosed with OUD. To address this, we conducted the largest transcriptomics study to date using postmortem brains from subjects with OUD. We focused on the dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (NAc), two regions heavily implicated in OUD. We discovered a high degree of overlap in transcripts between DLPFC and NAc in OUD, primarily associated with neuroinflammation. Moreover, additional transcripts were enriched for factors that control pro-inflammatory cytokine-mediated signaling and remodeling of the extracellular matrix (ECM). Our results also implicate a role for microglia as a critical driver for opioid-induced neuroplasticity. Overall, our findings reveal new connections between the brain’s immune system and opioid dependence in the human brain.

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Section: Enrichment Of Differentially Expressed Transcripts Involved mentioning

confidence: 91%

Transcriptional alterations in opioid use disorder reveal an interplay between neuroinflammation and synaptic remodeling

Seney

Moon-Kim

Glausier

et al. 2020

Preprint

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“…This assay was performed as described previously. ( 15,16 ) Global gene‐expression array data were available at the National Center for Biotechnology Information Gene Expression Omnibus under accession number http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE116689.…”

Section: Methodsmentioning

confidence: 99%

C/EBPα/miR‐7 Controls CD4+ T‐Cell Activation and Function and Orchestrates Experimental Autoimmune Hepatitis in Mice

Zhao

Chu

et al. 2021

Hepatology

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BaCKgRoUND aND aIMS:Increasing evidence in recent years has suggested that microRNA-7 (miR-7) is an important gene implicated in the development of various diseases including HCC. However, the role of miR-7 in autoimmune hepatitis (AIH) is unknown. appRoaCH aND ReSUltS: Herein, we showed that miR-7 deficiency led to exacerbated pathology in Concanavalin-A-induced murine acute autoimmune liver injury (ALI) model, accompanied by hyperactivation state of CD4 + T cells. Depletion of CD4 + T cells reduced the effect of miR-7 deficiency on the pathology of ALI. Interestingly, miR-7 deficiency elevated CD4 + T-cell activation, proliferation, and cytokine production in vitro. Adoptive cell transfer experiments showed that miR-7 def CD4 + T cells could exacerbate the pathology of ALI. Further analysis showed that miR-7 expression was up-regulated in activated CD4 + T cells. Importantly, the transcription of pre-miR-7b, a major resource of mature miR-7 in CD4 + T cells, was dominantly dependent on transcription factor CCAAT enhancer binding protein alpha (C/ EBPα), which binds to the core promoter region of the miR-7b gene. Global gene analysis showed that mitogen-activated protein kinase 4 (MAPK4) is a target of miR-7 in CD4 + T cells. Finally, the loss of MAPK4 could ameliorate the activation state of CD4 + T cells with or without miR-7 deficiency.Our studies document the important role of miR-7 in the setting of AIH induced by Concanavalin-A. Specifically, we provide evidence that the C/EBPα/miR-7 axis negatively controls CD4 + T-cell activation and function through MAPK4, thereby orchestrating experimental AIH in mice.CoNClUSIoNS: This study expands on the important role of miR-7 in liver-related diseases and reveals the value of the C/EBPα/miR-7 axis in CD4 + T-cell biological function for the pathogenesis of immune-mediated liver diseases.

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“…Importantly, altered expression of miR‐7 could affect the transduction of TLR4 signalling and expression of related inflammatory cytokines such as TNF‐α, IL‐1β and IL‐6, indicating that miR‐7 is an important negative regulator in TLR4 signalling pathway. Interestingly, our new evidence also found that miR‐7, synergistic with RORα, controls the pathology of brain tissue inflammation, which related to enhanced function of neuron cells, 37 indicating that the biological role of miR‐7 is different in distinct in vivo and in vitro experimental settings, in which there are the complex interaction networks among distinct cells expressing miRNA molecules and their target genes. So, we presume that these finding might support the fact that miR‐7 could be an important intrinsic regulator in TLR signalling pathway including TLR4.…”

Section: Discussionmentioning

confidence: 63%

MicroRNA‐7 negatively regulates Toll‐like receptor 4 signaling pathway through FAM177A

et al. 2020

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Toll-like receptor (TLR) 4 signalling is critical for innate immunoinflammatory response and widely triggers the development of various types of clinical diseases. MicroRNA-7 (miR-7) is well documented to play an important regulatory role in various biological events. However, the exact role of miR-7 in TLR4 signalling pathway remains to be fully elucidated. In the present study, we found that miR-7 expression in TLR4 signallingactivated bone marrow-derived macrophages (BMDMs) stimulated by LPS was dramatically increased. Importantly, miR-7 deficiency significantly enhanced the production of related inflammatory cytokines including IL-1b, IL-6 and IL-12, as well as TNF-a, on LPS-activated BMDMs, accompanied by elevated transduction of TLR4 signalling including Myd88-dependent and Myd88-independent pathways, whereas miR-7 overexpression significantly decreased the transduction of TLR4 signalling and the production of related inflammatory cytokines. Mechanistically, we identified family with sequence similarity 177, member A (FAM177A) as a novel target molecule of miR-7. Furthermore, down-regulation of FAM177A using RNAi could impair the transduction of TLR4 signalling. Finally, down-regulation of FAM177A also reversed the effect of miR-7 deficiency on TLR4 signalling transduction and production of related inflammatory cytokines on BMDMs. Therefore, we provide the new evidence that miR-7 acts as a novel negative fine-tuner in regulating TLR4 signalling pathways by targeting FAM177A, which might throw light on the basal understanding on the regulatory mechanism of TLR4 signalling and benefit the development of therapeutic strategies against related clinical diseases.

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MicroRNA-7, synergizes with RORα, negatively controls the pathology of brain tissue inflammation

Cited by 18 publications

References 71 publications

Transcriptional alterations in opioid use disorder reveal an interplay between neuroinflammation and synaptic remodeling

Transcriptional alterations in opioid use disorder reveal an interplay between neuroinflammation and synaptic remodeling

C/EBPα/miR‐7 Controls CD4+ T‐Cell Activation and Function and Orchestrates Experimental Autoimmune Hepatitis in Mice

MicroRNA‐7 negatively regulates Toll‐like receptor 4 signaling pathway through FAM177A

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