ArticleArthritis research & therapy2023
SMAD2 inhibits pyroptosis of fibroblast-like synoviocytes and secretion of inflammatory factors via the TGF-β pathway in rheumatoid arthritis.
Article in Arthritis research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 25 citations in OpenAlex.
- Generation of DFNA5-deficient chickens reveals a species-specific role of pyroptosis in avian antiviral immunity.Transgenic research · 2026Article
- Cellular crosstalk and signaling networks in the rheumatoid arthritis synovial microenvironment.Journal of translational medicine · 2026Review
- The "Tianyu" Formulation Alleviates Rheumatoid Arthritis by Modulating the NLRP3/Caspase-1/GSDMD-Mediated Pyroptosis Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Transcription factor SPI1 drives immunosuppressive CD45RMD open · 2026Article
- Revisiting osteoarthritis pathogenesis through the lens of cGAS-STING: Mitochondrial damage, pyroptosis, and inflammatory cascades.Journal of orthopaedic translation · 2026Review
- Frontier research on mechanisms of bone destruction in rheumatoid arthritis.Frontiers in cell and developmental biology · 2026Review
- AGTR1 inhibits pyroptosis and inflammatory cytokine secretion in rheumatoid arthritis fibroblast-like synoviocytes through the TGF-β pathway.American journal of translational research · 2026Article
- Joint Tissues: Convergence and Divergence of the Pathogenetic Mechanisms of Rheumatoid Arthritis and Osteoarthritis.International journal of molecular sciences · 2025Review
- Natural and synthetic potential drug leads for rheumatoid arthritis probing innovative target: mitochondrial dysfunction and NLRP3 inflammasome activation.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Mechanistic and therapeutic insights into the function of different cell death modalities in rheumatoid arthritis: emphasis on the crosstalk with non-coding RNAs.Frontiers in immunology · 2025Review
- Programmed Cell Death in Rheumatoid Arthritis.Journal of inflammation research · 2025Review
- Fibroblast-like synoviocytes-derived exosomal circFTO deteriorates rheumatoid arthritis by enhancing N6-methyladenosine modification of SOX9 in chondrocytes.Arthritis research & therapy · 2024Article
- Cytoplasmic DNA and AIM2 inflammasome in RA: where they come from and where they go?Frontiers in immunology · 2024Review
- A Novel Bioswitchable miRNA Mimic Delivery System: Therapeutic Strategies Upgraded from Tetrahedral Framework Nucleic Acid System for Fibrotic Disease Treatment and Pyroptosis Pathway Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- New Potentiality of Bioactive Substances: Regulating the NLRP3 Inflammasome in Autoimmune Diseases.Nutrients · 2023Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveRheumatoid arthritis (RA) is a chronic, progressive autoimmune disease. Over-activation of fibroblast-like synoviocytes is responsible for the hyperplasia of synovium and destruction of cartilage and bone and pyroptosis of FLS plays a key role in those pathological processes during RA. This study investigated the detailed mechanisms that SMAD2 regulates the pyroptosis of FLS and secretion of inflammatory factors in rheumatoid arthritis.
methodsWe collected synovial tissues of RA patients and FLS-RA and cultured FLS for detection of expression of SMAD2. ASC, NLRP3, cleaved-caspase-1, and GSDMD-N were detected by Western blot after overexpression of SMAD2. Besides, flow cytometry, electron microscope, ELISA, HE staining, and Safranin O staining were performed to further demonstrate that SMAD2 can affect the pyroptosis of FLS-RA.
resultsThe expression of SMAD2 was down-regulated in synovial tissues of RA patients and FLS-RA. Overexpression of SMAD2 can inhibit the expression of ASC, NLRP3, cleaved-caspase-1, and GSDMD-N. Flow cytometry and electron microscope further demonstrated that SMAD2 attenuated pyroptosis of FLS-RA. In addition, overexpression of SMAD2 also inhibited inflammatory factors such as IL-1β, IL-18, IL-6, and IL-8 secretion and release of LDH. Besides, overexpression of SMAD2 can reverse the decrease of p-SMAD2 and TGF-TGF-β induced by nigericin. In vivo experiments on CIA rats further demonstrated that overexpression of SMAD2 by local intra-articular injection of LV-SMAD2 can effectively alleviate joint redness, swelling, and destruction of cartilage and bones.
conclusionSMAD2 inhibited FLS-RA pyroptosis by down-regulating of NLRP3 inflammasomes (NLRP3, ASC, and caspase-1 complex) and eased the secretion of inflammatory factors via the TGF-β signaling pathway, thereby improving the symptom of RA. We hope that this study may provide a new research idea for RA and a potential target for the treatment of RA.
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