ArticleFrontiers in immunology2017
RANTES/CCL5 Induces Collagen Degradation by Activating MMP-1 and MMP-13 Expression in Human Rheumatoid Arthritis Synovial Fibroblasts.
Article in Frontiers in immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- Efficacy and safety of TCMs with anti-inflammatory effect in patients with rheumatoid arthritis: A network meta-analysis.Frontiers in immunology · 2023Pooled it
- Investigating the Link Between Specific Signaling Molecules (CCL5, CCR5, CXCR4, BMPR2) and Cardiac Health Indicators in Rheumatoid Arthritis Individuals: A Cross-Sectional Study.Health science reports · 2026Article
- Inflammation-driven bone erosion and reactive remodeling in experimental arthritis revealed by cortical bone surface analysis.Arthritis research & therapy · 2026Article
- New Paradigm for Rheumatoid Arthritis Treatment: A Review of 'Crosstalk' Mechanism of Multi-Targeted Intervention on Cytokine/Chemokine Networks by Chinese Medicine.Chinese journal of integrative medicine · 2026Review
- Alpha2EQ downregulates proinflammatory cytokine and chemokine gene expression in cultured synovial fibroblasts.American journal of veterinary research · 2026Article
- Adipose tissue harbors pathogenic T cells in obesity that exacerbate inflammatory arthritis.The Journal of experimental medicine · 2025Article
- GZMK Facilitates Experimental Rheumatoid Arthritis Progression by Interacting with CCL5 and Activating the ERK Signaling.Inflammation · 2025Article
- Crosstalk between ferroptosis and NLRP3, a possible therapeutic target in experimentally-induced rheumatoid arthritis: role of P2Y12R inhibition in modulating P53/SLC7A11/ALOX15 signaling.Inflammopharmacology · 2025Article
- Regulation of matrix metalloproteinase-13 in cancer: Signaling pathways and non-coding RNAs in tumor progression and therapeutic targeting.World journal of clinical oncology · 2025Review
- Hand Osteoarthritis: Molecular Mechanisms, Randomized Controlled Trials, and the Future of Targeted Treatment.International journal of molecular sciences · 2025Review
- Discovery of MMP1 Inhibitors from Dandelion using Molecular Simulation and Bioactivity Test.Current topics in medicinal chemistry · 2025Article
- Pararamosis, a Neglected Tropical Disease Induced byInternational journal of molecular sciences · 2024Article
- Identification of potential immune-related genes and infiltrations in temporomandibular joint osteoarthritis.Annals of medicine and surgery (2012) · 2024Article
- Identification of Hub Genes and Prediction of Targeted Drugs for Rheumatoid Arthritis and Idiopathic Pulmonary Fibrosis.Biochemical genetics · 2024Article
- Integration of single-cell and bulk RNA sequencing revealed immune heterogeneity and its association with disease activity in rheumatoid arthritis patients.Immunologic research · 2024Article
- Synoviocytes assist in modulating the effect of Ross River virus infection in micromass-cultured primary human chondrocytes.Journal of medical microbiology · 2024Article
- Regulation of cytokine and chemokine expression by histone lysine methyltransferase MLL1 in rheumatoid arthritis synovial fibroblasts.Scientific reports · 2024Article
- Cell-specific gene networks and drivers in rheumatoid arthritis synovial tissues.Frontiers in immunology · 2024Article
- Identification and Verification of Novel Biomarkers Involving Rheumatoid Arthritis with Multimachine Learning Algorithms: An In Silicon and In Vivo Study.Mediators of inflammation · 2024Article
- A targeted proteomics screen reveals serum and synovial fluid proteomic signature in patients with gout.Frontiers in immunology · 2024Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Regulated on activation, normal T expressed, and secreted (RANTES)/CC ligand 5 (CCL5) participates in rheumatoid arthritis (RA) pathogenesis by facilitating leukocyte infiltration, however, its other pathological functions are not fully defined in RA. In the present study, we evaluated the effect of RANTES/CCL5 on tissue degrading enzymes matrix metalloproteinase-1 (MMP-1) and MMP-13 expression and its contribution to the progressive joint damage by RA synovial fibroblasts (RASFs). Our results showed that RANTES/CCL5 dose dependently induced MMP-1 and MMP-13 expression in monolayers and three-dimensional (3D) micromass of human RASFs, which correlated with an increase in collagenase activity. This activation by RANTES/CCL5 was observed in RASF, but not in osteoarthritis SFs (OASFs). Evaluation of the signaling events showed that RANTES/CCL5 selectively activated PKCδ, JNK, and ERK proteins to induce MMP expression in human RASFs. Pretreatment with a functional antagonist (Met-RANTES) or heparinase III [an enzyme that selectively digests heparan sulfate proteoglycans (HSPGs)] completely abrogated RANTES/CCL5-induced MMP-1 and MMP-13 expression. Interestingly, the inhibition of RANTES/CCL5 using small-interfering RNA approach reduced the ability of interleukin-1β (IL-1β) to induce MMP-1 and MMP-13 expression, asserting its mediatory role in tissue remodeling. In the inhibitor study, only the selective inhibition of HSPGs or PKCδ, ERK, and JNK markedly inhibited RANTES/CCL5-induced MMP-1 and MMP-13 production. Circular dichroism spectroscopy results demonstrated the degradation of collagen triple-helical structure upon exposure to the conditioned media from RANTES/CCL5 stimulated RASFs, which was reverted by a broad-spectrum MMP inhibitor (GM6001). These findings suggest that RANTES/CCL5 not only upregulates MMP-1 and MMP-13 expression by partly utilizing HSPGs and/or PKCδ-JNK/ERK pathways but also mediates IL-1β-induced MMP-1 and MMP-13 expression.
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