Background: The regulatory mechanisms of the expression of connective tissue growth factor/CCN family member 2 (CTGF/CCN2) in human articular chondrocytes have not been clarified. We investigated the effect of prostaglandin E2 (PGE2) on CTGF/CCN2 expression in chondrocytes.
Findings: Articular cartilage samples were obtained from patients with osteoarthritis (OA) and chondrocytes were isolated and cultured in vitro. Chondrocytes were stimulated with PGE2, PGE receptor (EP)-specific agonists, or interleukin (IL)-1. CTGF expression was analyzed using quantitative polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay. The inhibitory effects of EP receptor antagonists (for EP2 and EP4) against PGE2 stimulation were also investigated. Stimulation of chondrocytes with PGE2 or IL-1 significantly suppressed CTGF expression. The suppressive effect of PGE2 was reproduced by EP2/EP4 receptor agonists but not by EP1/EP3 receptor agonists, and was partially blocked by an EP4 receptor antagonist, suggesting that the EP4 receptor has a dominant role.
Conclusions: PGE2 may be involved in the regulation of CTGF/CCN2 expression in human articular chondrocytes via the EP4 receptor. Elucidation of EP4-mediated signaling in chondrocytes may contribute to a better understanding of the effects of PGE2 in arthritis.
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http://dx.doi.org/10.1186/1756-0500-3-5 | DOI Listing |
Environ Microbiol
December 2024
School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
Oxylipin signalling is central in biology, mediating processes such as cellular homeostasis, inflammation and molecular signalling. It may also facilitate inter-partner communication in the cnidarian-dinoflagellate symbiosis, though this aspect remains understudied. In this study, four oxylipin receptors were characterised using immunohistochemistry and immunoblotting in the sea anemone Exaiptasia diaphana ('Aiptasia'): Prostaglandin E2 receptor 2 (EP2) and 4 (EP4), Transient Receptor Potential cation channel A1 (TRPA1) and Glutamate Receptor Ionotropic, Kainate 2 (GRIK2).
View Article and Find Full Text PDFCancer Res Commun
December 2024
Kanazawa University, Kanazawa, Ishikawa, Japan.
Missense-type p53 mutations have shown to acquire novel oncogenic roles through gain-of-function mechanism. However, there is an intratumor heterogeneity in stabilization of mutant p53 protein, and it has not been well understood about interaction of p53-stabilized and p53-destabilized cells in the same tumors. We established mouse intestinal tumor-derived organoids carrying Apcδ716, KrasG12D, and Tgfbr2-/- mutations with Trp53R270H or Trp53Null mutation (AKTPR270H and AKTPNull, respectively).
View Article and Find Full Text PDFJ Cell Mol Med
December 2024
Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Clin Cancer Res
December 2024
Department of Clinical Research, Rottapharm Biotech, Monza, Italy and University of Milano - Bicocca, School of Medicine, Milan, Italy, Italy.
Purpose: Novel combinations are required to overcome resistance to immune checkpoint inhibitors (ICIs) in proficient mismatch repair (pMMR) or microsatellite stable (MSS) metastatic colorectal cancer (mCRC). We aimed to determine whether vorbipiprant, a prostaglandin EP4 receptor antagonist, can convert immune-resistant mCRC into a tumor responsive to anti-PD-1 inhibition.
Patients And Methods: This phase 1b/2a prospective, open-label, single-arm trial followed a 3 + 3 dose escalation and dose optimization design.
Cell Signal
February 2025
Division of Cell Signalling and Immunology, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. Electronic address:
The EP4 (prostaglandin E2) receptor plays a crucial role in myogenesis and skeletal muscle regeneration, yet its involvement in regulating insulin-dependent metabolic pathways is not well characterised. Our research investigates the expression of EP4 in rat skeletal L6 myotubes and its impact on insulin signalling. We found that activation of EP4 by selective agonists disrupts insulin signalling and insulin-stimulated glucose uptake.
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