ArticleCellular & molecular immunology2018
TXNDC5 synergizes with HSC70 to exacerbate the inflammatory phenotype of synovial fibroblasts in rheumatoid arthritis through NF-κB signaling.
Article in Cellular & molecular immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- Comparison of the efficacy of TXNDC5 monoclonal antibody versus conventional drugs in the treatment of intestinal fibrosis associated with inflammatory bowel disease.Journal of molecular histology · 2026Article
- Endogenous Expression of HSP70 and Thioredoxin-1 During Methamphetamine-Induced Degeneration.Biomedicines · 2026Article
- Endoplasmic reticulum stress exacerbates ischemia-reperfusion-induced pulmonary endothelial barrier dysfunction by activating TXNDC5.Journal of advanced research · 2026Article
- SEM1 Downregulates HSPA8 to Suppress TLR4/MyD88/NF-κB Signaling and Alleviate Myocardial I/R Injury.International journal of molecular sciences · 2026Article
- Absence of Thioredoxin Domain Containing 5 Improves Glucose Tolerance and Insulin Sensitivity in Male Mice.International journal of molecular sciences · 2026Article
- TXNDC5 in POAG: Promoting Extracellular Matrix Protein Accumulation and Raising Intraocular Pressure.Investigative ophthalmology & visual science · 2026Article
- Targeting Senescence with Apigenin Improves Chemotherapeutic Efficacy and Ameliorates Age-Related Conditions in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Acidosis regulates immune progression in rheumatoid arthritis by promoting the expression of cytokines and co-stimulatory molecules in synovial fibroblasts.Molecular medicine (Cambridge, Mass.) · 2025Article
- Endoplasmic reticulum protein TXNDC5 modulates thyroid eye disease TGF-β1-induced myofibroblast transdifferentiation.BMJ open ophthalmology · 2024Article
- SHISA3 Reprograms Tumor-Associated Macrophages Toward an Antitumoral Phenotype and Enhances Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Thioredoxin Domain Containing 5 (TXNDC5): Friend or Foe?Current issues in molecular biology · 2024Review
- The role and mechanism of TXNDC5 in disease progression.Frontiers in immunology · 2024Review
- Transcriptomic Analyses of Neurotoxic Astrocytes Derived from Adult Triple Transgenic Alzheimer's Disease Mice.Journal of molecular neuroscience : MN · 2023Article
- The novel role of ER protein TXNDC5 in the pathogenesis of organ fibrosis: mechanistic insights and therapeutic implications.Journal of biomedical science · 2022Review
- The role and mechanism of TXNDC5 in diseases.European journal of medical research · 2022Review
- Inhibition of TXNDC5 attenuates lipopolysaccharide-induced septic shock by altering inflammatory responses.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Euphorbia factor L3 ameliorates rheumatoid arthritis by suppressing the inflammatory response by targeting Rac family small GTPase 1.Bioengineered · 2022Article
- Thioredoxin Domain Containing 5 Suppression Elicits Serum Amyloid A-Containing High-Density Lipoproteins.Biomedicines · 2022Article
- Stress-induced phosphoprotein 1 restrains spinal cord ischaemia-reperfusion injury by modulating NF-κB signalling.Journal of cellular and molecular medicine · 2021Article
- Inhibition of heat shock protein family A member 8 attenuates spinal cord ischemia-reperfusion injury via astrocyte NF-κB/NLRP3 inflammasome pathway : HSPA8 inhibition protects spinal ischemia-reperfusion injury.Journal of neuroinflammation · 2021Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The upregulated expression of thioredoxin domain-containing protein 5 (TXNDC5) is associated with rheumatoid arthritis in patients and model mice. However, the underlying mechanism by which TXNDC5 influences the pathological activation of rheumatoid arthritis synovial fibroblasts (RASFs) remains unknown. In this study, we show that TXNDC5 expression in RASFs and their cytokine production are significantly upregulated in response to LPS, TNF-α and IL-6, but suppressed by transfection with TXNDC5-siRNA. TXNDC5 is further validated as the direct target of NF-κB signaling. Mechanistically, TXNDC5 directly interacts with heat shock cognate 70 protein (HSC70) to sequester it in the cytoplasm, and HSC70 silencing exerts the same effects as TXNDC5 on the biological activity of RASFs (for example, decreased cell viability, invasion and cytokine production). Furthermore, HSC70 activates NF-κB signaling by destabilizing IκBβ protein in the absence of LPS or facilitating its nuclear translocation in the presence of LPS. Importantly, TXNDC5 can also regulate the activity of NF-κB signaling in a HSC70-IκBβ-dependent manner. Taken together, by linking HSC70 and NF-κB signaling, TXNDC5 plays a pro-inflammatory role in RASFs, highlighting a potential approach to treat RA by blocking the TXNDC5/HSC70 interaction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.