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Genistein inhibits angiogenesis developed during rheumatoid arthritis through the IL-6/JAK2/STAT3/VEGF signalling pathway

Cheng, W-X., Huang, H., Chen, J-H., Zhang, T-T., Zhu, G-Y., Zheng, Z-T., Lin, J-T., Hu, Y-P., Zhang, Y., Bai, X-L., Wang, Y., Xu, Z-W., Song, B., Mao, Y-Y., Yang, F. and Zhang, P. 2019. Genistein inhibits angiogenesis developed during rheumatoid arthritis through the IL-6/JAK2/STAT3/VEGF signalling pathway. Journal of Orthopaedic Translation 10.1016/j.jot.2019.07.007

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Abstract

Background Angiogenesis plays an important role in the development of rheumatoid arthritis (RA), which increases the supply of nutrients, cytokines, and inflammatory cells to the synovial membrane. Genistein (GEN), a soy-derived isoflavone, has been validated that can effectively inhibit the angiogenesis of several tumours. We thus carried out a study in vitro to investigate the effect of GEN in vascular endothelial growth factor (VEGF) expression and angiogenesis induced by the inflammatory environment of RA. Methods MH7A cells were used to verify whether GEN can inhibit the expression of VEGF in MH7A cells under inflammatory conditions and demonstrate the mechanism. EA.hy926 ​cells were used to verify whether GEN can inhibit the migration and tube formation of vascular endothelial cells in inflammatory environment. Results GEN dose-dependently inhibited the expression and secretion of interleukin (IL)-6 and VEGF, as well as the nucleus translocation of Signal transducer and activator of transcription 3 (STAT3) in MH7A. Furthermore, GEN inhibited IL-6–induced vascular endothelial cell migration and tube formation in vitro. Conclusion GEN inhibits IL-6–induced VEGF expression and angiogenesis partially through the Janus kinase 2 (JAK2)/STAT3 pathway in RA, which has provided a novel insight into the antiangiogenic activity of GEN in RA.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Dentistry
Publisher: Elsevier
ISSN: 2214-031X
Date of First Compliant Deposit: 30 September 2019
Date of Acceptance: 28 July 2019
Last Modified: 30 Sep 2019 11:00
URI: http://orca.cf.ac.uk/id/eprint/125725

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