ArticleAnnals of the rheumatic diseases2019
PTPN14 phosphatase and YAP promote TGFβ signalling in rheumatoid synoviocytes.
Article in Annals of the rheumatic diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 58 citations in OpenAlex.
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- Analysis of knockout mice reveals critical female-specific roles for the Hippo pathway component PTPN14.Genes & development · 2025Article
- KLF11 alleviates rheumatoid arthritis by regulating M1 macrophage polarization via downregulation of YAP1 expression.Arthritis research & therapy · 2025Article
- Senkyunolide I prevent chondrocytes from oxidative stress through Nrf2/HO-1 signaling pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- LRRC4 Deficiency Drives Premature Ovarian Insufficiency by Disrupting Metabolic Homeostasis in Granulosa Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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- MST1 interactomes profiling across cell death in esophageal squamous cell carcinoma.Medical review (2021) · 2024Article
- Quantitative characterization of immune cells by measuring cellular signal transduction pathway activity.Scientific reports · 2024Article
- The Hippo signalling pathway in bone homeostasis: Under the regulation of mechanics and aging.Cell proliferation · 2024Review
- Suppression of YAP Ameliorates Cartilage Degeneration in Ankle Osteoarthritis via Modulation of the Wnt/β-Catenin Signaling Pathway.Calcified tissue international · 2024Article
- Suppression of NUPR1 in fibroblast-like synoviocytes reduces synovial fibrosis via the Smad3 pathway.Journal of translational medicine · 2024Article
- Yap drives the development of cardiovascular disease in patients with rheumatoid arthritis.Journal of medical biochemistry · 2024Article
- The immunometabolic function of VGLL3 and female-biased autoimmunity.Immunometabolism (Cobham, Surrey) · 2024Review
- GRK2 mediated degradation of SAV1 initiates hyperplasia of fibroblast-like synoviocytes in rheumatoid arthritis.Acta pharmaceutica Sinica. B · 2024Article
- The Hippo-YAP Signaling Pathway in Osteoarthritis and Rheumatoid Arthritis.Journal of inflammation research · 2024Review
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Authors and funding
24 authors at 5 institutions in 4 countries.
Funding
Abstract
objectiveWe aimed to understand the role of the tyrosine phosphatase PTPN14-which in cancer cells modulates the Hippo pathway by retaining YAP in the cytosol-in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA).
methodsGene/protein expression levels were measured by quantitative PCR and/or Western blotting. Gene knockdown in RA FLS was achieved using antisense oligonucleotides. The interaction between PTPN14 and YAP was assessed by immunoprecipitation. The cellular localisation of YAP and SMAD3 was examined via immunofluorescence. SMAD reporter studies were carried out in HEK293T cells. The RA FLS/cartilage coimplantation and passive K/BxN models were used to examine the role of YAP in arthritis.
resultsRA FLS displayed overexpression of PTPN14 when compared with FLS from patients with osteoarthritis (OA). PTPN14 knockdown in RA FLS impaired TGFβ-dependent expression of MMP13 and potentiation of TNF signalling. In RA FLS, PTPN14 formed a complex with YAP. Expression of PTPN14 or nuclear YAP-but not of a non-YAP-interacting PTPN14 mutant-enhanced SMAD reporter activity. YAP promoted TGFβ-dependent SMAD3 nuclear localisation in RA FLS. Differences in epigenetic marks within Hippo pathway genes, including YAP, were found between RA FLS and OA FLS. Inhibition of YAP reduced RA FLS pathogenic behaviour and ameliorated arthritis severity.
conclusionIn RA FLS, PTPN14 and YAP promote nuclear localisation of SMAD3. YAP enhances a range of RA FLS pathogenic behaviours which, together with epigenetic evidence, points to the Hippo pathway as an important regulator of RA FLS behaviour.
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