Vascular Endothelial Growth Factor Is Regulated by the Canonical and Noncanonical Transforming Growth Factor-β Pathway in Synovial Fibroblasts Derived from Osteoarthritis Patients
| Autor: | Shotaro Takano, Shintaro Shoji, Masashi Takaso, Manabu Mukai, Makoto Itakura, Jun Aikawa, Hiroyuki Sekiguchi, Dai Iwase, Kentaro Uchida, Gen Inoue |
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| Rok vydání: | 2019 |
| Předmět: |
030203 arthritis & rheumatology
0301 basic medicine Article Subject General Immunology and Microbiology Kinase p38 mitogen-activated protein kinases Growth factor medicine.medical_treatment lcsh:R lcsh:Medicine General Medicine Molecular biology General Biochemistry Genetics and Molecular Biology Vascular endothelial growth factor Blot 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine chemistry medicine Phosphorylation Signal transduction Transforming growth factor |
| Zdroj: | BioMed Research International, Vol 2019 (2019) |
| ISSN: | 2314-6141 2314-6133 |
| Popis: | Background. Previous studies suggest the presence of an association of vascular endothelial growth factor (VEGF) with osteoarthritis (OA) severity and pain in patients with knee OA. VEGF expression in human synovial fibroblasts (SFs) is induced by transforming growth factor-beta (TGFβ). However, the signaling pathway governing TGFβ-mediated regulation of VEGF in SFs has not been identified. Methods. OA patients who underwent total knee arthroplasty had their synovial tissue (SYT) extracted and the constituent SFs cultured. The cells were stimulated with culture medium (control), human recombinant TGFβ (hrTGFβ), hrTGFβ + ALK5 inhibitor SB505124, hrTGFβ + transforming growth factor activating kinase 1 (TAK1) inhibitor (5Z)-7-oxozeaenol, or hrTGFβ + p38 inhibitor SB203580 for 6 h. VEGF mRNA expression in SFs was examined using real-time polymerase chain reaction and VEGF protein production in the cell supernatant was examined using enzyme-linked immunosorbent assay. Additionally, phosphorylated levels of SMAD2 and p38 were examined using western blotting. Results. ALK5 (SB505124) and TAK1 (5Z-oxozeaenol) inhibitors completely suppressed TGFβ-induced VEGF mRNA expression and VEGF protein production. Both SB505124 and 5Z-oxozeaenol also suppressed SMAD2 and p38 phosphorylation. The p38 inhibitor (SB203580) partially inhibited TGFβ-mediated VEGF mRNA and VEGF protein production. Conclusion. TGFβ-mediated regulation of VEGF expression and VEGF protein production in the SYT of OA patients occurs through both the canonical and noncanonical pathway. |
| Databáze: | OpenAIRE |
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