ArticleMolecular and cellular biochemistry2013
PI3 kinase/Akt/HIF-1α pathway is associated with hypoxia-induced epithelial-mesenchymal transition in fibroblast-like synoviocytes of rheumatoid arthritis.
Article in Molecular and cellular biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 50 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 101 citations in OpenAlex.
- Trial
- Hypoxia as an amplifier of synovial inflammation in rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
- Flavonoids and flavonoid-based nanoparticles for the treatment of arthritis.Inflammopharmacology · 2025Review
- The role of hypoxic microenvironment in rheumatoid arthritis.Frontiers in immunology · 2025Review
- Article
- Mammalian STE20-like kinase 1 inhibits synoviocytes activation in rheumatoid arthritis through mitochondrial dysfunction mediated by SIRT3/mTOR axis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Synergistic chemotherapy/PTT/oxygen enrichment by multifunctional liposomal polydopamine nanoparticles for rheumatoid arthritis treatment.Asian journal of pharmaceutical sciences · 2024Article
- The role of hypoxic microenvironment in autoimmune diseases.Frontiers in immunology · 2024Review
- Involvement of Epithelial-Mesenchymal Transition (EMT) in Autoimmune Diseases.International journal of molecular sciences · 2023Review
- New Targets and Strategies for Rheumatoid Arthritis: From Signal Transduction to Epigenetic Aspect.Biomolecules · 2023Review
- Receptor tyrosine kinase C-kit promotes a destructive phenotype of FLS in osteoarthritis via intracellular EMT signaling.Molecular medicine (Cambridge, Mass.) · 2023Article
- Signaling pathways in rheumatoid arthritis: implications for targeted therapy.Signal transduction and targeted therapy · 2023Review
- Artemisitene suppresses rheumatoid arthritis progression via modulating METTL3-mediated N6-methyladenosine modification of ICAM2 mRNA in fibroblast-like synoviocytes.Clinical and translational medicine · 2022Article
- Cellular metabolic adaptations in rheumatoid arthritis and their therapeutic implications.Nature reviews. Rheumatology · 2022Review
- Metabolites as drivers and targets in rheumatoid arthritis.Clinical and experimental immunology · 2022Article
- Tofacitinib May Inhibit Myofibroblast Differentiation from Rheumatoid-Fibroblast-like Synoviocytes Induced by TGF-β and IL-6.Pharmaceuticals (Basel, Switzerland) · 2022Article
- High prevalence of rheumatoid arthritis and its risk factors among Tibetan highlanders living in Tsarang, Mustang district of Nepal.Journal of physiological anthropology · 2022Article
- Baicalein Induces Apoptosis of Rheumatoid Arthritis Synovial Fibroblasts through Inactivation of the PI3K/Akt/mTOR Pathway.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Emerging role of hypoxia-inducible factor-1α in inflammatory autoimmune diseases: A comprehensive review.Frontiers in immunology · 2022Review
- Cadherin Signaling in Cancer and Autoimmune Diseases.International journal of molecular sciences · 2021Review
Corrections and comments
- Retraction · 2024-06-07Concerns/Issues about Image · Duplication of/in Image · Error in Image · Euphemisms for Duplication · Investigation by Journal/Publisher · Original Data and/or Images not Provided and/or not Available · Results Not Reproducible · · See also: https://pubpeer.com/publications/FD956C830D85FC75F1A05E50A1E564
- Retracted
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Migration and invasion of fibroblast-like synoviocytes (FLSs) are critical in the pathogenesis of rheumatoid arthritis (RA). Hypoxic conditions are present in RA joints, and hypoxia has been extensively studied in angiogenesis and inflammation. However, its effect on the migration and invasion of RA-FLSs remains unknown. In this study, we observed that RA-FLSs exposed to hypoxic conditions experienced epithelial-mesenchymal transition (EMT), with increased cell migration and invasion. We demonstrated that hypoxia-induced EMT was accompanied by increased hypoxia-inducible factor (HIF)-1α expression and activation of Akt. After knockdown or inhibition of HIF-1α in hypoxia by small interfering RNA or genistein (Gen) treatment, the EMT transformation and invasion ability of FLSs were regained. HIF-1α could be blocked by phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, indicating that HIF-1α activation was regulated by the PI3K/Akt pathway. Administration of LY294002 (20 mg/kg, intra-peritoneally) twice weekly and Gen (25 mg/kg, by gavage) daily for 3 weeks from day 20 after primary immunization in a collagen-induced arthritis rat model, markedly alleviated the clinical signs, radiology progression, synovial hyperplasia, and inflammatory cells infiltration of joints. Thus, results of this study suggest that activation of the PI3K/Akt/HIF-1α pathway plays a pivotal role in mediating hypoxia-induced EMT transformation and invasion of RA-FLSs under hypoxia.
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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.