CCL5 and related genes might be the potential diagnostic biomarkers for the therapeutic strategies of rheumatoid arthritis

Huang, Yiyan; Zheng, Songyuan; Wang, Ran; Tang, Cuiping; Zhu, Ji-Xiao; Li, Juan

doi:10.1007/s10067-019-04533-1

Cited by 16 publications

(14 citation statements)

References 35 publications

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“…RANTES (or CCL5) was the only molecule that showed a significant difference between the CIA and CIA+FD groups. A recent report on bioinformatic analysis of human RA gene expression data indicates that CCL5 might have a negative impact on the development of RA [61], while another recent report in mouse indicates that peritoneal levels of several CC chemokines, including CCL5, could be related with mouse strain susceptibility to experimental arthritis [62]. However, as in our study, neither group had a significant difference to control, and so the biological meaning of this result remains unclear.…”

Section: Discussioncontrasting

confidence: 69%

The Systemic Immune Response to Collagen-Induced Arthritis and the Impact of Bone Injury in Inflammatory Conditions

Teixeira

Silva

Almeida

et al. 2019

IJMS

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Rheumatoid arthritis (RA) is a systemic disease that affects the osteoarticular system, associated with bone fragility and increased risk of fractures. Herein, we aimed to characterize the systemic impact of the rat collagen-induced arthritis (CIA) model and explore its combination with femoral bone defect (FD). The impact of CIA on endogenous mesenchymal stem/stromal cells (MSC) was also investigated. CIA induction led to enlarged, more proliferative, spleen and draining lymph nodes, with altered proportion of lymphoid populations. Upon FD, CIA animals increased the systemic myeloid cell proportions, and their expression of co-stimulatory molecules CD40 and CD86. Screening plasma cytokine/chemokine levels showed increased tumor necrosis factor-α (TNF-α), Interleukin (IL)-17, IL-4, IL-5, and IL-12 in CIA, and IL-2 and IL-6 increased in CIA and CIA+FD, while Fractalkine and Leptin were decreased in both groups. CIA-derived MSC showed lower metabolic activity and proliferation, and significantly increased osteogenic and chondrogenic differentiation markers. Exposure of control-MSC to TNF-α partially mimicked the CIA-MSC phenotype in vitro. In conclusion, inflammatory conditions of CIA led to alterations in systemic immune cell proportions, circulating mediators, and in endogenous MSC. CIA animals respond to FD, and the combined model can be used to study the mechanisms of bone repair in inflammatory conditions.

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Section: Discussioncontrasting

confidence: 69%

The Systemic Immune Response to Collagen-Induced Arthritis and the Impact of Bone Injury in Inflammatory Conditions

Teixeira

Silva

Almeida

et al. 2019

IJMS

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“…RANTES, also known as chemokine C-C motif ligand 5 (CCL5), which is classified as a chemokine encoded by the CCL5 gene, and acts as an important inflammatory cytokine that promotes the progression of RA 51-54. Our results have shown that acid-induced activation of ASIC1a enhanced RANTES expression by mediating Ca 2+ influx, and its effect was significantly stronger than that of IL-8, MIP-1a, ICAM-1, TNF RI, and TNF RII.…”

Section: Resultsmentioning

confidence: 99%

ASIC1a induces synovial inflammation via the Ca²⁺/NFATc3/ RANTES pathway

et al. 2020

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Rationale: Synovial inflammation is one of the main pathological features of rheumatoid arthritis (RA) and is a key factor leading to the progression of RA. Understanding the regulatory mechanism of synovial inflammation is crucial for the treatment of RA. Acid-sensing ion channel 1a (ASIC1a) is an H+-gated cation channel that promotes the progression of RA, but the role of ASIC1a in synovial inflammation is unclear. This study aimed to investigate whether ASIC1a is involved in the synovial inflammation and explore the underlying mechanisms in vitro and in vivo.Methods: The expression of ASIC1a and nuclear factor of activated T cells (NFATs) were analyzed by Western blotting, immunofluorescence, and immunohistochemistry both in vitro and in vivo. The Ca2+ influx mediated by ASIC1a was detected by calcium imaging and flow cytometry. The role of ASIC1a in inflammation was studied in rats with adjuvant-induced arthritis (AA). Inflammatory cytokine profile was analyzed by protein chip in RA synovial fibroblasts (RASF) and verified by a magnetic multi-cytokine assay and ELISA. The NFATc3-regulated RANTES (Regulated upon activation, normal T cell expressed and secreted) gene transcription was investigated by ChIP-qPCR and dual-luciferase reporter assay.Results: The expression of ASIC1a was significantly increased in human RA synovial tissues and primary human RASF as well as in ankle synovium of AA rats. Activated ASIC1a mediated Ca2+ influx to increase [Ca2+]i in RASF. The activation/overexpression of ASIC1a in RASF up-regulated the expression of inflammatory cytokines RANTES, sTNF RI, MIP-1a, IL-8, sTNF RII, and ICAM-1 among which RANTES was increased most remarkably. In vivo, ASIC1a promoted inflammation, synovial hyperplasia, articular cartilage, and bone destruction, leading to the progression of AA. Furthermore, activation of ASIC1a upregulated the nuclear translocation of NFATc3, which bound to RANTES promoter and directly regulated gene transcription to enhance RANTES expression.Conclusion: ASIC1a induces synovial inflammation, which leads to the progression of RA. Our study reveals a novel RA inflammation regulatory mechanism and indicates that ASIC1a might be a potential therapeutic target for RA.

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“…Up to now, various biomarkers have been identified to be associated with rheumatoid arthritis and may be selected as therapeutic targets, but the detailed mechanism of gene regulation leading to disease progression remains elusive [28,29].…”

Section: Discussionmentioning

confidence: 99%

“…There is no doubt that understanding diseases at the molecular level will help to improve their diagnosis and treatment [ 26 , 27 ]. Up to now, various biomarkers have been identified to be associated with rheumatoid arthritis and may be selected as therapeutic targets, but the detailed mechanism of gene regulation leading to disease progression remains elusive [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Bioinformatics Analysis Reveals Hub Genes and Inflammation State of Rheumatoid Arthritis

Ren

Du³

et al. 2020

BioMed Research International

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by erosive arthritis, which has not been thoroughly cured yet, and standardized treatment is helpful for alleviating clinical symptoms. Here, various bioinformatics analysis tools were comprehensively utilized, aiming to identify critical biomarkers and possible pathogenesis of RA. Three gene expression datasets profiled by microarray were obtained from GEO database. Dataset GSE55235 and GSE55457 were merged for subsequent analyses. We identified differentially expressed genes (DEGs) in RStudio with limma package, performing functional enrichment analysis based on GSEA software and clusterProfiler package. Next, protein-protein interaction (PPI) network was set up through STRING database and Cytoscape. Moreover, CIBERSORT website was used to assess the inflammatory state of RA. Finally, we validated the candidate hub genes with dataset GSE77298. As a result, we identified 106 DEGs (72 upregulated and 34 downregulated genes). Through GO, KEGG, and GSEA analysis, we found that DEGs were mainly involved in immune response and inflammatory signaling pathway. With the help of Cytoscape software and MCODE plug-in, the most prominent subnetwork was screened out, containing 14 genes and 45 edges. For ROC curve analysis, eight genes with AUC >0.80 were considered as hub genes of RA. In conclusion, compared with healthy controls, the DEGs and their closely related biological functions were analyzed, and we held that chemokines and immune cells infiltration promote the progression of rheumatoid arthritis. Targeting the eight biomarkers we identified may be useful for the diagnosis and treatment of rheumatoid arthritis.

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CCL5 and related genes might be the potential diagnostic biomarkers for the therapeutic strategies of rheumatoid arthritis

Cited by 16 publications

References 35 publications

The Systemic Immune Response to Collagen-Induced Arthritis and the Impact of Bone Injury in Inflammatory Conditions

The Systemic Immune Response to Collagen-Induced Arthritis and the Impact of Bone Injury in Inflammatory Conditions

ASIC1a induces synovial inflammation via the Ca²⁺/NFATc3/ RANTES pathway

Comprehensive Bioinformatics Analysis Reveals Hub Genes and Inflammation State of Rheumatoid Arthritis

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CCL5 and related genes might be the potential diagnostic biomarkers for the therapeutic strategies of rheumatoid arthritis

Cited by 16 publications

References 35 publications

The Systemic Immune Response to Collagen-Induced Arthritis and the Impact of Bone Injury in Inflammatory Conditions

The Systemic Immune Response to Collagen-Induced Arthritis and the Impact of Bone Injury in Inflammatory Conditions

ASIC1a induces synovial inflammation via the Ca2+/NFATc3/ RANTES pathway

Comprehensive Bioinformatics Analysis Reveals Hub Genes and Inflammation State of Rheumatoid Arthritis

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ASIC1a induces synovial inflammation via the Ca²⁺/NFATc3/ RANTES pathway