ArticleThe Journal of experimental medicine2012
A novel pathogenic role of the ER chaperone GRP78/BiP in rheumatoid arthritis.
Article in The Journal of experimental medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 157 citations in OpenAlex.
- Unveiling the dark side of glucose-regulated protein 78 (GRP78) in cancers and other human pathology: a systematic review.Molecular medicine (Cambridge, Mass.) · 2023Pooled it
- Inhibiting endoplasmic reticulum stress and unfolded protein response: an effective strategy for chemoprevention of hepatocarcinogenesis.Molecular and cellular biochemistry · 2026Article
- Spatial and functional characterization of ER stress proteins links fibroblast plasticity and proliferative processes in human osteoarthritic synovitis.Cell death and differentiation · 2026Article
- Endoplasmic reticulum stress and apoptosis-associated biomarkers in rheumatoid arthritis: an exploratory case-control study.Rheumatology international · 2026Observational
- Regulation of Endoplasmic Reticulum Stress Suppresses Early Pro-Tumorigenic Events During N-Nitrosodiethylamine-Induced Hepatocarcinogenesis.Journal of biochemical and molecular toxicology · 2026Article
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- GRP78 in human diseases: From molecular chaperone to therapeutic target.Theranostics · 2026Review
- Galectin-9 inhibition of the MIF-CD74/CD44 pathway suppresses chronic arthritis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The Differential Expressions and Associations of Intracellular and Extracellular GRP78/Bip with Disease Activity and Progression in Rheumatoid Arthritis.Bioengineering (Basel, Switzerland) · 2025Article
- MiR-378 exaggerates angiogenesis and bone erosion in collagen-induced arthritis mice by regulating endoplasmic reticulum stress.Cell death & disease · 2024Article
- Synoviocyte detachment: an overlooked yet crucial histological aspect in rheumatoid arthritis.BMC musculoskeletal disorders · 2024Article
- The Functions of SARS-CoV-2 Receptors in Diabetes-Related Severe COVID-19.International journal of molecular sciences · 2024Review
- Suppression of NUPR1 in fibroblast-like synoviocytes reduces synovial fibrosis via the Smad3 pathway.Journal of translational medicine · 2024Article
- Ferroptosis and endoplasmic reticulum stress in rheumatoid arthritis.Frontiers in immunology · 2024Review
- Serum and urine lipidomic profiles identify biomarkers diagnostic for seropositive and seronegative rheumatoid arthritis.Frontiers in immunology · 2024Article
- Identification of MYH9 as a key regulator for synoviocyte migration and invasion through secretome profiling.Annals of the rheumatic diseases · 2023Article
- Role of high-temperature requirement serine protease A 2 in rheumatoid inflammation.Arthritis research & therapy · 2023Article
- CDK7/GRP78 signaling axis contributes to tumor growth and metastasis in osteosarcoma.Oncogene · 2022Article
- Endoplasmic reticulum stress triggered autophagy and regulated the phenotype transformation of rheumatoid arthritis synovial fibroblasts via the IRE1/JNK pathway.Annals of translational medicine · 2022Article
- Endoplasmic Reticulum Stress, Oxidative Stress, and Rheumatic Diseases.Antioxidants (Basel, Switzerland) · 2022Review
31 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 7 institutions in 3 countries.
Funding
Abstract
An accumulation of misfolded proteins can trigger a cellular survival response in the endoplasmic reticulum (ER). In this study, we found that ER stress-associated gene signatures were highly expressed in rheumatoid arthritis (RA) synoviums and synovial cells. Proinflammatory cytokines, such as TNF and IL-1β, increased the expression of GRP78/BiP, a representative ER chaperone, in RA synoviocytes. RA synoviocytes expressed higher levels of GRP78 than osteoarthritis (OA) synoviocytes when stimulated by thapsigargin or proinflammatory cytokines. Down-regulation of Grp78 transcripts increased the apoptosis of RA synoviocytes while abolishing TNF- or TGF-β-induced synoviocyte proliferation and cyclin D1 up-regulation. Conversely, overexpression of the Grp78 gene prevented synoviocyte apoptosis. Moreover, Grp78 small interfering RNA inhibited VEGF(165)-induced angiogenesis in vitro and also significantly impeded synoviocyte proliferation and angiogenesis in Matrigel implants engrafted into immunodeficient mice. Additionally, repeated intraarticular injections of BiP-inducible factor X, a selective GRP78 inducer, increased synoviocyte proliferation and angiogenesis in the joints of mice with experimental OA. In contrast, mice with Grp78 haploinsufficiency exhibited the suppression of experimentally induced arthritis and developed a limited degree of synovial proliferation and angiogenesis. In summary, this study shows that the ER chaperone GRP78 is crucial for synoviocyte proliferation and angiogenesis, the pathological hallmark of RA.
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