CCL7 promotes macrophage polarization and synovitis to exacerbate rheumatoid arthritis II
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PROVIDER: PRJNA1207088 | ENA |
REPOSITORIES: ENA
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Project description:Macrophage polarization and synovitis play significant roles in rheumatoid arthritis (RA). Chemokines are involved almost throughout the entire pathology of synovitis. However, the interaction between chemokines and macrophage polarization in RA has been seldom reported. This study found that chemokine C-C motif ligand 7 (CCL7) secreted by polarized M1 macrophages enhances M1 polarization, creating a positive feedback loop and revealing the role of CCL7 in the progression of rheumatoid arthritis. In this research, RNA sequencing indicated that M1 polarized macrophages secrete a large amount of CCL7, which further enhances M1 polarization. Through immunohistochemistry and enzyme-linked immunosorbent assay, it was found that the expression of CCL7 in the synovial tissue and serum of RA patients and mice was upregulated. Intra-articular injection of CCL7 recombinant protein exacerbated M1 polarization of macrophages, inflammation, fibrosis in the synovial tissue, and worsened arthritis pain in mice, which was improved after the injection of CCL7 neutralizing antibody. In addition, CCL7 promoted M1 polarization of macrophages and reversed the M2 polarization induced by IL-4, and it also promoted macrophage proliferation and migration. Although it had an inhibitory effect on chondrocyte activity, it did not show a significant impact on chondrocyte metabolism. Mechanistically, CCL7 targets CCR1 to promote M1 polarization of macrophages, a process partly mediated through the activation of the JAK2/STAT1 pathway. When stimulated by CCL7, macrophages secreted a vast amount of pro-inflammatory factors, exacerbating synovitis and cartilage damage, leading to the aggravation of RA disease. Our research established a positive feedback loop between M1 polarization of macrophages and CCL7, indicating that blocking CCL7 could improve the progression of RA, suggesting CCL7 as a potential target for RA treatment.
2025-01-08 | GSE267151 | GEO
Project description:Macrophage polarization and synovitis play significant roles in rheumatoid arthritis (RA). Chemokines are involved almost throughout the entire pathology of synovitis. However, the interaction between chemokines and macrophage polarization in RA has been seldom reported. This study found that chemokine C-C motif ligand 7 (CCL7) secreted by polarized M1 macrophages enhances M1 polarization, creating a positive feedback loop and revealing the role of CCL7 in the progression of rheumatoid arthritis. In this research, RNA sequencing indicated that M1 polarized macrophages secrete a large amount of CCL7, which further enhances M1 polarization. Through immunohistochemistry and enzyme-linked immunosorbent assay, it was found that the expression of CCL7 in the synovial tissue and serum of RA patients and mice was upregulated. Intra-articular injection of CCL7 recombinant protein exacerbated M1 polarization of macrophages, inflammation, fibrosis in the synovial tissue, and worsened arthritis pain in mice, which was improved after the injection of CCL7 neutralizing antibody. In addition, CCL7 promoted M1 polarization of macrophages and reversed the M2 polarization induced by IL-4, and it also promoted macrophage proliferation and migration. Although it had an inhibitory effect on chondrocyte activity, it did not show a significant impact on chondrocyte metabolism. Mechanistically, CCL7 targets CCR1 to promote M1 polarization of macrophages, a process partly mediated through the activation of the JAK2/STAT1 pathway. When stimulated by CCL7, macrophages secreted a vast amount of pro-inflammatory factors, exacerbating synovitis and cartilage damage, leading to the aggravation of RA disease. Our research established a positive feedback loop between M1 polarization of macrophages and CCL7, indicating that blocking CCL7 could improve the progression of RA, suggesting CCL7 as a potential target for RA treatment.
2025-01-08 | GSE285977 | GEO
Project description:CCL7 promotes macrophage polarization and synovitis to exacerbate rheumatoid arthritis
| PRJNA1109863 | ENA
Project description:Disease activity drives transcriptomic heterogeneity in early untreated rheumatoid synovitis
| PRJNA937236 | ENA
Project description:The purpose of this study was to investigate the transcriptomic heterogeneity in synovial tissue of early untreated rheumatoid arthritis patients in association with clinical data
2023-05-31 | GSE225731 | GEO
Project description:Increasing evidence shows that adipokines play a vital role in the development of rheumatoid arthritis (RA). Fatty acid-binding protein 4 (FABP4), a novel adipokine that regulates inflammation and angiogenesis, has been extensively studied in a variety of organs and diseases. However, the effect of FABP4 on RA remains unclear. Here, we found that FABP4 expression was upregulated in synovial M1-polarized macrophages in RA. The increase in FABP4 promoted synovitis, angiogenesis, and cartilage degradation to exacerbate RA progression in vivo and in vitro, whereas BMS309403 (a FABP4 inhibitor) and anagliptin (dipeptidyl peptidase 4 inhibitor) inhibited FABP4 expression in serum and synovial M1-polarized macrophages in mice to alleviate RA progression. Further studies showed that constitutive activation of mammalian target of rapamycin complex 1 (mTORC1) by TSC1 deletion specifically in the myeloid lineage regulated FABP4 expression in macrophages to exacerbate RA progression in mice. In contrast, inhibition of mTORC1 by ras homolog enriched in brain (Rheb1) disruption specifically in the myeloid lineage reduced FABP4 expression in macrophages to attenuate RA development in mice. Our findings established an essential role of FABP4 that is secreted by M1-polarized macrophages in synovitis, angiogenesis, and cartilage degradation in RA. BMS309403 and anagliptin inhibited FABP4 expression in synovial M1-polarized macrophages to alleviate RA development. Hence, FABP4 may represent a potential target for RA therapy.
| S-EPMC9213409 | biostudies-literature
Project description:Activated fibroblast-like synoviocytes (FLS) are drivers of synovitis and structural joint damage in rheumatoid arthritis (RA). Despite the use of disease-modifying drugs, only about 50% of RA patients reach remission in real-world settings. We used an unbiased approach to investigate the effects of standard-of-care methotrexate (MTX) and a Janus kinase inhibitor, tofacitinib (TOFA), on gene expression in RA-FLS, in order to identify untargeted disease mediators.
2024-10-04 | GSE266310 | GEO
Project description:ST36 acupuncture ameliorates immune cell proliferation and polarization by inhibiting sympathetic activity in rheumatoid arthritis
| PRJNA1112165 | ENA
Project description:Tenosynovial giant-cell tumor (TGCT) and pigmented villonodular synovitis (PVNS) are related conditions with features of both reactive inflammatory disorders and clonal neoplastic proliferations. Chromosomal translocations involving chromosome 1p13 have been reported in both TGCT and PVNS. We confirm that translocations involving 1p13 are present in a majority of cases of TGCT and PVNS and show that CSF1 is the gene at the chromosome 1p13 breakpoint. In some cases of both TGCT and PVNS, CSF1 is fused to COL6A3 (2q35). The CSF1 translocations result in overexpression of CSF1. In cases of TGCT and PVNS carrying this translocation, it is present in a minority of the intratumoral cells, leading to CSF1 expression only in these cells, whereas the majority of cells express CSF1R but not CSF1, suggesting a tumor-landscaping effect with aberrant CSF1 expression in the neoplastic cells, leading to the abnormal accumulation of nonneoplastic cells that form a tumorous mass. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Computed
2006-02-24 | E-GEOD-4166 | biostudies-arrayexpress
Project description:Rheumatoid synoviocytes, which consist of fibroblast-like synoviocytes (FLS) and synovial macrophages (SM), are crucial for the progression of rheumatoid arthritis (RA). Particularly, FLS of RA patients (RA-FLS) exhibit invasive characteristics reminiscent of cancer cells, destroying cartilage and bone, although it remains unresolved how RA-FLS exhibit invasive phenotype. RA-FLS and SM originate differently from mesenchymal and myeloid cells, respectively, but share many pathologic functions. However, the molecular signatures and biological networks representing the distinct and shared features of the two cell types are unknown. Presently, we performed global transcriptome profiling of FLS and SM obtained from RA and osteoarthritis patients. By comparing the transcriptomes, we identified distinct molecular signatures and cellular processes defining invasiveness of RA-FLS and pro-inflammatory properties of RA synovial macrophages (RA-SM), respectively. Interestingly, under interleukin1β-stimulated condition, RA-FLS newly acquired pro-inflammatory signature mimicking RA-SM without losing invasive properties. We next reconstructed a network model that delineates the shared, RA-FLS-dominant (invasive), and RA-SM-dominant (inflammatory) processes. From the network model, we selected 13 genes, including POSTN and TWIST1, as novel regulator candidates responsible for FLS invasiveness. Of note, POSTN and TWIST1 expressions were elevated in independent RA-FLS and were further instigated by interleukin1β. In vitro functional assays demonstrated the requirement of POSTN and TWIST1 for migration and invasion of RA-FLS stimulated with interleukin1β. Taken together, our systems approach to rheumatoid synovitis provides a basis for identifying novel regulators responsible for pathological features of RA-FLS and RA-SM, demonstrating how a certain type of cells acquires functional redundancy under chronic inflammatory conditions. To identify molecular signatures of FLS and MLS in RA joints, we isolated FLS from synovial tissues of RA and osteoarthritis (OA) patients, obtained synovial macrophages from synovial fluid of RA patients, and differentiated control macrophages from peripheral blood of healthy subjects. Also, we stimulated FLS with IL1β, and then analyzed gene expression profiles of both IL1β-stimulated RA-FLS and OA-FLS
2014-01-09 | E-GEOD-49604 | biostudies-arrayexpress