ArticleAnnals of the rheumatic diseases2023
PU.1 promotes development of rheumatoid arthritis via repressing FLT3 in macrophages and fibroblast-like synoviocytes.
Article in Annals of the rheumatic diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 62 citations in OpenAlex.
- Biomimetic M2 exosome-based dual-drug nanoplatform for combined immunomodulation and bone protection in rheumatoid arthritis.Bioactive materials · 2026Article
- Multi-Technique Integration Identifies O-GlcNAc Transferase in Fibroblast-Like Synoviocytes as a Therapeutic Target for Rheumatoid Arthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Activating transcription factors: Orchestrators of macrophage biology in pathological settings (Review).International journal of molecular medicine · 2026Review
- PU.1 aggravates hepatic sinusoidal obstruction syndrome by upregulating PTBP1 and activating the Wnt/β-catenin pathway.Histology and histopathology · 2026Article
- Folate-modified biomimetic nanovesicles loaded with a PU.1 inhibitor alleviate atherosclerosis by suppressing inflammation.Journal of nanobiotechnology · 2025Article
- Novel molecular mechanisms of FLT3 deregulation: from the acute myeloid leukemia experience to therapeutic insights in acute lymphoblastic leukemia.Molecular cancer · 2025Review
- GRK2-mediated phosphorylation and de-succinylation of PKM2 reduce macrophage glycolysis in rheumatoid arthritis.Acta pharmacologica Sinica · 2025Article
- Near-infrared light-driven metabolic reprogramming of synoviocytes for the treatment of rheumatoid arthritis.Nature communications · 2025Article
- Spi1 aggravates neuropathic pain by modulating Clec7a-mediated neuroinflammation and microglial phagocytosis.The journal of headache and pain · 2025Article
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- The role of SPI1/VSIG4/THBS1 on glioblastoma progression through modulation of the PI3K/AKT pathway.Journal of advanced research · 2025Article
- GRK2 activates TRAF2-NF-Acta pharmaceutica Sinica. B · 2025Article
- Defining gastric cancer ecology: the crucial roles of TREM2Communications biology · 2025Article
- Quercetagetin alleviates inflammatory osteoclastogenesis and collagen antibody-induced arthritis via Nrf2 signaling and Pten/AKT/Nfatc1 axis.Arthritis research & therapy · 2025Article
- Dual Targeting Biomimetic Carrier-Free Nanosystems for Photo-Chemotherapy of Rheumatoid Arthritis via Macrophage Apoptosis and Re-Polarization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Synovial macrophage diversity and activation of M-CSF signaling in post-traumatic osteoarthritis.eLife · 2025Article
- Treatment of rheumatoid arthritis using dual-targeted and dual-response intelligent micelles: a "three birds with one stone" strategy.Journal of nanobiotechnology · 2025Article
- Comprehensive multiomics analysis identifies PYCARD as a key pyroptosis-related gene in osteoarthritis synovial macrophages.Frontiers in immunology · 2025Article
- RNA modification: a promising code to unravel the puzzle of autoimmune diseases and CD4Frontiers in immunology · 2025Review
- Identification and experimental validation of PYCARD as a crucial PANoptosis-related gene for immune response and inflammation in COPD.Apoptosis : an international journal on programmed cell death · 2024Article
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesTo uncover the function and underlying mechanism of an essential transcriptional factor, PU.1, in the development of rheumatoid arthritis (RA).
methodsThe expression and localisation of PU.1 and its potential target, FMS-like tyrosine kinase 3 (FLT3), in the synovium of patients with RA were determined by western blot and immunohistochemical (IHC) staining. UREΔ (with PU.1 knockdown) and FLT3-ITD (with FLT3 activation) mice were used to establish collagen antibody-induced arthritis (CAIA). For the in vitro study, the effects of PU.1 and FLT3 on primary macrophages and fibroblast-like synoviocytes (FLS) were investigated using siRNAs. Mechanistically, luciferase reporter assays, western blotting, FACS and IHC were conducted to show the direct regulation of PU.1 on the transcription of FLT3 in macrophages and FLS. Finally, a small molecular inhibitor of PU.1, DB2313, was used to further illustrate the therapeutic effects of DB2313 on arthritis using two in vivo models, CAIA and collagen-induced arthritis (CIA).
resultsThe expression of PU.1 was induced in the synovium of patients with RA when compared with that in osteoarthritis patients and normal controls. FLT3 and p-FLT3 showed opposite expression patterns compared with PU.1 in RA. The CAIA model showed that PU.1 was an activator, whereas FLT3 was a repressor, of the development of arthritis in vivo. Moreover, results from in vitro assays were consistent with the in vivo results: PU.1 promoted hyperactivation and inflammatory status of macrophages and FLS, whereas FLT3 had the opposite effects. In addition, PU.1 inhibited the transcription of FLT3 by directly binding to its promoter region. The PU.1 inhibitor DB2313 clearly alleviated the effects on arthritis development in the CAIA and CIA models.
conclusionsThese results support the role of PU.1 in RA and may have therapeutic implications by directly repressing FLT3. Therefore, targeting PU.1 might be a potential therapeutic approach for RA.
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