Cheng Wen-Xiang, Huang Huan, Chen Jian-Hai, Zhang Tian-Tian, Zhu Guo-Yuan, Zheng Zheng-Tan, Lin Jie-Tao, Hu Yi-Ping, Zhang Yong, Bai Xue-Ling, Wang Yan, Xu Zhan-Wang, Song Bing, Mao Yi-Ying, Yang Fei, Zhang Peng
Center for Translational Medicine Research and Development, Shen Zhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, Guangdong, 518055, China.
University of Chinese Academy of Sciences, Beijing, 10049, China.
J Orthop Translat. 2019 Aug 23;22:92-100. doi: 10.1016/j.jot.2019.07.007. eCollection 2020 May.
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.
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.
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.
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.
Our study provides scientific guidance for the clinical translational research of GEN in the RA treatment.
血管生成在类风湿关节炎（RA）的发展中起重要作用，它增加了滑膜的营养物质、细胞因子和炎症细胞的供应。染料木黄酮（GEN）是一种源自大豆的异黄酮，已被证实可有效抑制多种肿瘤的血管生成。因此，我们进行了一项体外研究，以探讨GEN对RA炎症环境诱导的血管内皮生长因子（VEGF）表达和血管生成的影响。
使用MH7A细胞验证GEN是否能在炎症条件下抑制MH7A细胞中VEGF的表达并阐明其机制。使用EA.hy926细胞验证GEN是否能在炎症环境中抑制血管内皮细胞的迁移和管腔形成。
GEN剂量依赖性地抑制MH7A中白细胞介素（IL）-6和VEGF的表达与分泌，以及信号转导和转录激活因子3（STAT3）的核转位。此外，GEN在体外抑制IL-6诱导的血管内皮细胞迁移和管腔形成。
GEN在RA中部分通过Janus激酶2（JAK2）/STAT3途径抑制IL-6诱导的VEGF表达和血管生成，这为GEN在RA中的抗血管生成活性提供了新的见解。
我们的研究为GEN在RA治疗中的临床转化研究提供了科学指导。
