ArticleArthritis research & therapy2015
Expression of Semaphorin 4A and its potential role in rheumatoid arthritis.
Article in Arthritis research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 54 citations in OpenAlex.
- SEMA4A signaling in macrophage subpopulations and its implication in osteoarthritis.Frontiers in immunology · 2026Article
- Study on the pathogenesis of PLXNB1 gene in olfactory dysfunction of allergic rhinitis.PloS one · 2026Article
- AP39 suppresses osteoclast differentiation and neural factor expression under inflammatory condition.Journal of orthopaedic surgery and research · 2025Article
- Single-cell transcriptomics reveals dynamic reprogramming of testicular immunity inZoological research · 2025Article
- Semaphorin4B is elevated in rheumatoid arthritis and enhances the inflammatory phenotype of macrophages and fibroblast-like synoviocytes.Arthritis research & therapy · 2025Article
- Niche-derived Semaphorin 4A safeguards functional identity of myeloid-biased hematopoietic stem cells.Nature aging · 2025Article
- Muscle quality index correlates with arthritis: a cross-sectional study from NHANES 2011-2014.Frontiers in medicine · 2025Article
- Conventional DMARDs therapy decreases disease activity and inflammation in newly diagnosed patients with rheumatoid arthritis by increasing FoxP3, Sema-3A, and Nrp-1 gene expression.Inflammopharmacology · 2024Article
- The emerging role of the semaphorin family in cartilage and osteoarthritis.Histochemistry and cell biology · 2024Review
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- Review
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- Single-cell RNA Sequencing Reveals Novel Cellular Factors for Response to Immunosuppressive Therapy in Aplastic Anemia.HemaSphere · 2023Article
- Relevance of circulating Semaphorin 4A for rheumatoid arthritis response to treatment.Scientific reports · 2023Article
- Plexin B1 controls Treg numbers, limits allergic airway inflammation, and regulates mucins.Frontiers in immunology · 2023Article
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- Semaphorins in immune cell function, inflammatory and infectious diseases.Current research in immunology · 2023Review
- The Role of Semaphorins and Their Receptors in Innate Immune Responses and Clinical Diseases of Acute Inflammation.Frontiers in immunology · 2021Review
- FTY720 Inhibits the Development of Collagen-Induced Arthritis in Mice by Suppressing the Recruitment of CD4Drug design, development and therapy · 2021Article
- Semaphorin4A-Plexin D1 Axis Induces Th2 and Th17 While Represses Th1 Skewing in an Autocrine Manner.International journal of molecular sciences · 2020Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionSemaphorin 4A (Sema4A) plays critical roles in many physiological and pathological processes including neuronal development, angiogenesis, immune response regulation, autoimmunity, and infectious diseases. The present study aimed to investigate its expression and biological activity in rheumatoid arthritis (RA).
methodsRNA and protein were isolated from synovial tissues in RA and osteoarthritis (OA) patients. Treatment with recombinant human Sema4A (rhSema4A) or small interfering RNA (siRNA) was applied to examine its effect on the biological activity of synovial fibroblasts of RA (RASFs). Expression of Sema4A and NF-κB were measured by quantitative RT-PCR (qRT-PCR) and Western blot after lipopolysaccharide (LPS) stimulation. Chromatin immunoprecipitation (ChIP) and siRNA targeting p50 and p60 were applied to detect the regulation of Nuclear factor kappa (NF-κB) on Sema4A. Sema4A, interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) secretion were measured by ELISA-based assays.
resultsIncreased levels of Sema4A were detected in the synovial tissue and fluid of patients with RA compared with those with OA. Furthermore, synovial fluid level of Sema4A correlated with Disease Activity Score (DAS) in RA. Treatment with rhSema4A promoted invasion of RASFs by upregulating the expression of Matrix metallopeptidase3 (MMP3), MMP9, alpha-smooth muscle actin(α-SMA), and Vimentin, and exacerbated inflammation by promoting the production of IL-6 in RASFs, as well as IL-1β and TNF-α in THP-1 cells. The induction of IL-6 and TNF-α by Sema4A was confirmed at the protein level in fluid samples from patients with RA. Knock-down experiments showed the participation of Plexin B1 towards rhSema4A in the induction of cytokines. In addition, LPS stimulation induced Sema4A expression in RASFs in an NF-κB-dependent manner, and rhSema4A treatment could also activate NF-κB signaling.
conclusionsThese findings suggest an NF-κB-dependent modulation of Sema4A in the immune response. Further, increased expression of Sema4A is required to promote inflammation of RA.
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