ArticleArthritis & rheumatology (Hoboken, N.J.)2016
Receptor Protein Tyrosine Phosphatase α-Mediated Enhancement of Rheumatoid Synovial Fibroblast Signaling and Promotion of Arthritis in Mice.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Fibroblasts in immune responses, inflammatory diseases and therapeutic implications.Nature reviews. Rheumatology · 2025Review
- Enhancing the effectiveness of immunotherapy in rheumatoid arthritis by delaying immunosenescence triggered by fibroblast-like synoviocytes.Journal of orthopaedic surgery and research · 2025Review
- Article
- Clustering of phosphatase RPTPα promotes Src signaling and the arthritogenic action of synovial fibroblasts.Science signaling · 2023Article
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
- PTPα promotes fibroproliferative responses after acute lung injury.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Does a rare mutation in PTPRA contribute to the development of Parkinson's disease in an Australian multi-incident family?PloS one · 2022Article
- Ssu72 Dual-Specific Protein Phosphatase: From Gene to Diseases.International journal of molecular sciences · 2021Review
- Identification of novel loci controlling inflammatory bowel disease susceptibility utilizing the genetic diversity of wild-derived mice.Genes and immunity · 2020Article
- PTPRA facilitates cancer growth and migration via the TNF-α-mediated PTPRA-NF-κB pathway in MCF-7 breast cancer cells.Oncology letters · 2020Article
- Protein tyrosine phosphatase-α amplifies transforming growth factor-β-dependent profibrotic signaling in lung fibroblasts.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Restoring synovial homeostasis in rheumatoid arthritis by targeting fibroblast-like synoviocytes.Nature reviews. Rheumatology · 2020Review
- RPTPα phosphatase activity is allosterically regulated by the membrane-distal catalytic domain.The Journal of biological chemistry · 2020Article
- PTPN14 phosphatase and YAP promote TGFβ signalling in rheumatoid synoviocytes.Annals of the rheumatic diseases · 2019Article
- A Novel Phytochemical, DIM, Inhibits Proliferation, Migration, Invasion and TNF-α Induced Inflammatory Cytokine Production of Synovial Fibroblasts From Rheumatoid Arthritis Patients by Targeting MAPK and AKT/mTOR Signal Pathway.Frontiers in immunology · 2019Article
- The Importance of Tyrosine Phosphorylation Control of Cellular Signaling Pathways in Respiratory Disease: pY and pY Not.American journal of respiratory cell and molecular biology · 2018Review
- The immunoglobulin D Fc receptor expressed on fibroblast-like synoviocytes from patients with rheumatoid arthritis contributes to the cell activation.Acta pharmacologica Sinica · 2017Article
- Ssu72 attenuates autoimmune arthritis via targeting of STAT3 signaling and Th17 activation.Scientific reports · 2017Article
- AbnormalJCI insight · 2016Article
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 5 countries.
Funding
Abstract
objectiveDuring rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) critically promote disease pathogenesis by aggressively invading the extracellular matrix of the joint. The focal adhesion kinase (FAK) signaling pathway is emerging as a contributor to the anomalous behavior of RA FLS. The receptor protein tyrosine phosphatase α (RPTPα), which is encoded by the PTPRA gene, is a key promoter of FAK signaling. The aim of this study was to investigate whether RPTPα mediates FLS aggressiveness and RA pathogenesis.
methodsThrough RPTPα knockdown, we assessed FLS gene expression by quantitative polymerase chain reaction analysis and enzyme-linked immunosorbent assay, invasion and migration by Transwell assays, survival by annexin V and propidium iodide staining, adhesion and spreading by immunofluorescence microscopy, and activation of signaling pathways by Western blotting of FLS lysates. Arthritis development was examined in RPTPα-knockout (KO) mice using the K/BxN serum-transfer model. The contribution of radiosensitive and radioresistant cells to disease was evaluated by reciprocal bone marrow transplantation.
resultsRPTPα was enriched in the RA synovial lining. RPTPα knockdown impaired RA FLS survival, spreading, migration, invasiveness, and responsiveness to platelet-derived growth factor, tumor necrosis factor, and interleukin-1 stimulation. These phenotypes correlated with increased phosphorylation of Src on inhibitory Y(527) and decreased phosphorylation of FAK on stimulatory Y(397) . Treatment of RA FLS with an inhibitor of FAK phenocopied the knockdown of RPTPα. RPTPα-KO mice were protected from arthritis development, which was due to radioresistant cells.
conclusionBy regulating the phosphorylation of Src and FAK, RPTPα mediates proinflammatory and proinvasive signaling in RA FLS, correlating with the promotion of disease in an FLS-dependent model of RA.
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