ArticleArthritis and rheumatism2012
Methotrexate increases expression of cell cycle checkpoint genes via JNK activation.
Article in Arthritis and rheumatism, 2012. 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, 58 citations in OpenAlex.
- Identification of ferroptosis hub gene cDKN1A relating to immune microenvironment in rheumatoid arthritis via bioinformatic analysis and experimental verification.Clinical rheumatology · 2026Article
- Small-Molecule Strategies for Polymyalgia Rheumatica and Giant Cell Arteritis in Older Adults.Molecules (Basel, Switzerland) · 2026Review
- Methotrexate for Osteoarthritis: What Does the Evidence Say?Drugs & aging · 2026Review
- Protodioscin enhances Methotrexate-induced senescence and senolytic activity in HepG2 liver cancer spheroids by modulating cell cycle regulators and the TGF-β/p-Smad2-4 signaling pathway.Scientific reports · 2025Article
- Dapagliflozin targets the crosstalk between apoptosis, autophagy, and Hedgehog signaling pathways through AMPK activation in the adjuvant-induced arthritic rat model.Inflammopharmacology · 2025Article
- Organoid drug profiling identifies methotrexate as a therapy for SCCOHT, a rare pediatric cancer.Science advances · 2025Article
- Methotrexate promotes the release of granulocyte-macrophage colony-stimulating factor from rheumatoid arthritis fibroblast-like synoviocytes via autocrine interleukin-1 signaling.Arthritis research & therapy · 2024Article
- Review
- The Protective Effect of Roflumilast Against Acute Hepatotoxicity Caused by Methotrexate in Wistar Rats: In vivo Evaluation.Drug design, development and therapy · 2024Article
- Incomptine A Induces Apoptosis, ROS Production and a Differential Protein Expression on Non-Hodgkin's Lymphoma Cells.International journal of molecular sciences · 2021Article
- Methotrexate and its mechanisms of action in inflammatory arthritis.Nature reviews. Rheumatology · 2020Review
- Treatment effect of CDKN1A on rheumatoid arthritis by mediating proliferation and invasion of fibroblast-like synoviocytes cells.Clinical and experimental immunology · 2018Article
- Methotrexate inhibits effects of platelet-derived growth factor and interleukin-1β on rheumatoid arthritis fibroblast-like synoviocytes.Arthritis research & therapy · 2018Article
- Alpha2beta1 Integrin (VLA-2) Protects Activated Human Effector T Cells From Methotrexate-Induced Apoptosis.Frontiers in immunology · 2018Article
- Effects of methotrexate exposure on medaka (Journal of toxicologic pathology · 2017Article
- Expression of long non-coding RNAs in autoimmunity and linkage to enhancer function and autoimmune disease risk genetic variants.Journal of autoimmunity · 2017Article
- Methotrexate-coupled nanoparticles and magnetic nanochemothermia for the relapse-free treatment of T24 bladder tumors.International journal of nanomedicine · 2017Article
- Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases.Nature reviews. Rheumatology · 2017Review
- Pu-erh Tea Water Extract Mediates Cell Cycle Arrest and Apoptosis in MDA-MB-231 Human Breast Cancer Cells.Frontiers in pharmacology · 2017Article
- Effect of methotrexate exposure at middle gestation on the inner plate of the ocular cup and lens in the rat fetus.Journal of toxicologic pathology · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveTo assess defects in expression of critical cell cycle checkpoint genes and proteins in patients with rheumatoid arthritis (RA) relative to presence or absence of methotrexate (MTX) treatment, and to investigate the role of JNK in induction of these genes by MTX.
methodsFlow cytometric analysis was used to quantify changes in levels of intracellular proteins, measure reactive oxygen species (ROS), and determine apoptosis in different lymphoid populations. Quantitative reverse transcription-polymerase chain reaction was used to identify changes in cell cycle checkpoint target genes.
resultsRA patients expressed reduced baseline levels of MAPK9, TP53, CDKN1A, CDKN1B, CHEK2, and RANGAP1 messenger RNA (mRNA) and JNK total protein. The reduction in expression of mRNA for MAPK9, TP53, CDKN1A, and CDKN1B was greater in patients not receiving MTX than in those receiving low-dose MTX, with no difference in expression levels of CHEK2 and RANGAP1 mRNA between MTX-treated and non-MTX-treated patients. Further, JNK levels were inversely correlated with C-reactive protein levels in RA patients. In tissue culture, MTX induced expression of both p53 and p21 by JNK-2- and JNK-1-dependent mechanisms, respectively, while CHEK2 and RANGAP1 were not induced by MTX. MTX also induced ROS production, JNK activation, and sensitivity to apoptosis in activated T cells. Supplementation with tetrahydrobiopterin blocked these MTX-mediated effects.
conclusionOur findings support the notion that MTX restores some, but not all, of the proteins contributing to cell cycle checkpoint deficiencies in RA T cells, via a JNK-dependent pathway.
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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.