Gpr97/Adgrg3 ameliorates experimental autoimmune encephalomyelitis by regulating cytokine expression

Wang, Jinjin; Wang, Xiyi; Chen, Xuejiao; Shen, Lu; Kuang, Ying; Fei, Jian; Wang, Zhugang

doi:10.1093/abbs/gmy060

Cited by 16 publications

(7 citation statements)

References 45 publications

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“…MS is an immune-mediated inflammatory disease of the CNS (41, 42). The precise mechanisms of pathogenesis of MS remain unknown, although environmental as well as genetic components are believed to participate in this demyelinating disease (43).…”

Section: Discussionmentioning

confidence: 99%

Combination of Cannabinoids, Δ9- Tetrahydrocannabinol and Cannabidiol, Ameliorates Experimental Multiple Sclerosis by Suppressing Neuroinflammation Through Regulation of miRNA-Mediated Signaling Pathways

et al. 2019

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Multiple sclerosis (MS) is a chronic and disabling disorder of the central nervous system (CNS) characterized by neuroinflammation leading to demyelination. Recently a combination of Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) extracted from Cannabis has been approved in many parts of the world to treat MS-related spasticity. THC+CBD combination was also shown to suppresses neuroinflammation, although the mechanisms remain to be further elucidated. In the current study, we demonstrate that THC+CBD combination therapy (10 mg/kg each) but not THC or CBD alone, attenuates murine experimental autoimmune encephalomyelitis (EAE) by reducing neuroinflammation and suppression of Th17 and Th1 cells. These effects were mediated through CB1 and CB2 receptors inasmuch as, THC+CBD failed to ameliorate EAE in mice deficient in CB1 and CB2. THC+CBD treatment also caused a decrease in the levels of brain infiltrating CD4+ T cells and pro-inflammatory molecules (IL-17, INF-γ, TNF-α, IL-1β, IL-6, and TBX21), while increasing anti-inflammatory phenotype such as FoxP3, STAT5b, IL-4, IL-10, and TGF-β. Also, the brain-derived cells showed increased apoptosis along with decreased percentage in G0/G1 phase with increased percentage in G2/M phase of cell cycle. miRNA microarray analysis of brain-derived CD4+ T cells revealed that THC+CBD treatment significantly down-regulated miR-21a-5p, miR-31-5p, miR-122-5p, miR-146a-5p, miR-150-5p, miR-155-5p, and miR-27b-5p while upregulating miR-706-5p and miR-7116. Pathway analysis showed that majority of the down-regulated miRs targeted molecules involved in cycle arrest and apoptosis such as CDKN2A, BCL2L11, and CCNG1, as well as anti-inflammatory molecules such as SOCS1 and FoxP3. Additionally, transfection studies involving miR-21 and use of Mir21 −/− mice suggested that while this miR plays a critical role in EAE, additional miRs may also be involved in THC+CBD-mediated attenuation of EAE. Collectively, this study suggests that combination of THC+CBD suppresses neuroinflammation and attenuates clinical EAE development and that this effect is associated with changes in miRNA profile in brain-infiltrating cells.

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Section: Discussionmentioning

confidence: 99%

Combination of Cannabinoids, Δ9- Tetrahydrocannabinol and Cannabidiol, Ameliorates Experimental Multiple Sclerosis by Suppressing Neuroinflammation Through Regulation of miRNA-Mediated Signaling Pathways

et al. 2019

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“…Wang et. al have also verified that GPR97 regulated proinflammatory cytokine production in vitro culture assay and played an important role in the development of experimental autoimmune encephalomyelitis (EAE), which indicated that it may have a therapeutic potential for the treatment of CNS autoimmunity [ 31 ]. However, the role of GPR97 in CS is unclear and needs to be further explored.…”

Section: Discussionmentioning

confidence: 99%

Identification of Hub Genes Associated with Immune Infiltration in Cardioembolic Stroke by Whole Blood Transcriptome Analysis

Gao

Luo

et al. 2022

Disease Markers

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Cardioembolic stroke (CS) is the most common type of ischemic stroke in the clinic, leading to high morbidity and mortality worldwide. Although many studies have been conducted, the molecular mechanism underlying CS has not been fully grasped. This study was aimed at exploring the molecular mechanism of CS using comprehensive bioinformatics analysis and providing new insights into the pathophysiology of CS. We downloaded the public datasets GSE58294 and GSE16561. Differentially expressed genes (DEGs) were screened via the limma package using R software. CIBERSORT was used to estimate the proportions of 22 immune cells based on the gene expression profiling of CS patients. Using weighted gene correlation network analysis (WGCNA) to cluster the genes into different modules and detect relationships between modules and immune cell types, hub genes were identified based on the intersection of the protein-protein interaction (PPI) network analysis and WGCNA, and their clinical significance was then verified using another independent dataset GSE16561. Totally, 319 genes were identified as DEGs and 5413 genes were clustered into nine modules using WGCNA. The blue module, with the highest correlation coefficient, was identified as the key module associated with stroke, neutrophils, and B cells naïve. Based on the PPI analysis and WGCNA, five genes (MCEMP1, CLEC4D, GPR97, TSPAN14, and FPR2) were identified as hub genes. Correlation analysis indicated that hub genes had general association with infiltration-related immune cells. ROC analysis also showed they had potential clinical significance. The results were verified using another dataset, which were consistent with our analysis. Five crucial genes determined using integrative bioinformatics analysis might play significant roles in the pathophysiological mechanism in CS and be potential targets for pharmaceutic therapies.

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“…These colorectal cancer responsible genes might be candidate genes for CD. Recently, increasing evidence demonstrated that CXCL5 [379], S100A8 [380], LCN2 [381], CXCL1 [382], S100A9 [383], CXCL9 [384], CXCL11 [385], CXCL10 [386], NCF2 [387], SLC11A1 [388], GDF15 [389], IL1RN [390], STAT1 [391], CYP27B1 [392], SOCS3 [393], TLR8 [394], CD55 [395], ADGRG3 [396], CCL3 [397], FCGR2A [398], CCL2 [399], CD14 [400], IGFBP2 [401], PCSK9 [402], IDO1 [403], FOXP3 [404], CD163 [405], CCL7 [406], TLR2 [407], CCR2 [408], IL20RA [409], S100P [410], ADAMTS1 [411], TIMP1 [412], ICAM1 [413], IFNG (interferon gamma) [414], TREM2 [415], APOE (apolipoprotein E) [416], CCR1 [417], IL6 [418], CTHRC1 [419], PDCD1LG2 [420], CCL4 [421], IL11 [422], COL1A1 [423], MMP2 [424], IL1A [425], CD24 [426], POSTN (periostin) [427], GZMB (granzyme B) [428], BCL2A1 [429], CSF2 [430], TDO2 [431], CTLA4 [432], PADI4 [433], MPO (myeloperoxidase) [434], HP (haptoglobin) [435], MUC5B [436], MMP7 [437], PON3 [438], ABHD6 [439], AICDA (activation induced cytidine deaminase) [440], UGT1A6 [441], CYP2D6 [442], CYP3A5 [443], DGAT1 [444], FCRL4 [445], SLC22A4 [446], DPP4 [447], ACE (angiotensin I converting enzyme) [448], SLC5A11 [449], VIPR1 [450], FCRL3 [451], CD160 [452] and IL22RA2 […”

Section: Discussionmentioning

confidence: 99%

Identification of hub genes and key pathways in pediatric Crohn’s disease using next generation sequencing and bioinformatics analysis

Vastrad¹,

Vastrad²

2022

Preprint

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Pediatric Crohn's Disease (CD) also known as inflammatory bowel diseases, affects millions of people all over the world. The aim of this investigation is to identify the key genes in CD and uncover their potential functions. We downloaded the next generation sequencing (NGS) dataset GSE73374 from the Gene Expression Omnibus (GEO) database. The NGS dataset GSE73374 was used to screen differentially expressed genes (DEGs) between samples from patients with CD and healthy controls. Gene ontology (GO) and REACTOME pathway enrichment analyses were applied for the DEGs. Subsequently, a protein - protein interaction (PPI) network, modules, miRNA- hub gene regulatory network and TF - hub gene regulatory network were constructed to identify hub genes, miRNAs and TFs. Receiver operating characteristic curve (ROC) analysis was applied to validate the hub genes. A total of 957 DEGs were identified, including 478 up regulated genes and 479 down regulated genes. GO and REACTOME results suggested that several Go terms and pathways are involved in response to stimulus, extracellular region, signaling receptor binding, small molecule metabolic process, membrane, transporter activity, immune system and biological oxidations. The top centrality hub genes MDFI, MNDA, FBXO6, TFRC, STAT1, DPP4, MME, SLC39A4, APOA1 and TMEM25 were screened out as the critical genes among the DEGs from the PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network. This investigation identified key genes and signal pathways, which might help us improve our understanding of the molecular mechanisms of CD and identify some novel therapeutic targets for CD.

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Gpr97/Adgrg3 ameliorates experimental autoimmune encephalomyelitis by regulating cytokine expression

Cited by 16 publications

References 45 publications

Combination of Cannabinoids, Δ9- Tetrahydrocannabinol and Cannabidiol, Ameliorates Experimental Multiple Sclerosis by Suppressing Neuroinflammation Through Regulation of miRNA-Mediated Signaling Pathways

Combination of Cannabinoids, Δ9- Tetrahydrocannabinol and Cannabidiol, Ameliorates Experimental Multiple Sclerosis by Suppressing Neuroinflammation Through Regulation of miRNA-Mediated Signaling Pathways

Identification of Hub Genes Associated with Immune Infiltration in Cardioembolic Stroke by Whole Blood Transcriptome Analysis

Identification of hub genes and key pathways in pediatric Crohn’s disease using next generation sequencing and bioinformatics analysis

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