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

Wen-Xiang Cheng; Huan Huang; Jian-Hai Chen; Tian-Tian Zhang; Guo-Yuan Zhu; Zheng-Tan Zheng; Jie-Tao Lin; Yi-Ping Hu; Yong Zhang; Xue-Ling Bai; Yan Wang; Zhan-Wang Xu; Bing Song; Yi-Ying Mao; Fei Yang; Peng Zhang

doi:10.1016/j.jot.2019.07.007

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

J Orthop Translat. 2019 Aug 23:22:92-100. doi: 10.1016/j.jot.2019.07.007. eCollection 2020 May.

Authors

Wen-Xiang Cheng^{1

2

3}, Huan Huang^{1

2

4}, Jian-Hai Chen^{1

2}, Tian-Tian Zhang⁵, Guo-Yuan Zhu⁶, Zheng-Tan Zheng¹, Jie-Tao Lin^{1

2}, Yi-Ping Hu¹, Yong Zhang⁷, Xue-Ling Bai¹, Yan Wang¹, Zhan-Wang Xu⁸, Bing Song^{1

9}, Yi-Ying Mao¹⁰, Fei Yang¹¹, Peng Zhang^{1

2

12

13

3}

Affiliations

¹ Center for Translational Medicine Research and Development, Shen Zhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, Guangdong, 518055, China.
² University of Chinese Academy of Sciences, Beijing, 10049, China.
³ Shenzhen Engineering Research Center for Medical Bioactive Materials, Shenzhen, Guangdong, 518055, China.
⁴ Shenzhen Middle School, Shenzhen, Guangdong, 518001, China.
⁵ Department of Rheumatology, People's Hospital of Bao'an District, Shenzhen, Guangdong, 518128, China.
⁶ State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China.
⁷ Shenzhen Pingle Orthopaedic Hospital, Guangdong, 518000, China.
⁸ Department of Orthopaedic, The First Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Ji'nan, Shandong, 250000, China.
⁹ School of Dentistry, Cardiff University, Cardiff, Heath Park, CF23 6AL, UK.
¹⁰ Huizhou Second Maternal and Child Health Care Hospital, Huizhou, Guangdong, 516001, China.
¹¹ Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
¹² University of Chinese Academy of Sciences, Shenzhen Hospital, Shenzhen, 518000, China.
¹³ Department of Orthopedic, University of Chinese Academy of Sciences Shenzhen Hospital, 518000, Shenzhen, China.

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.

The translational potential of this article: Our study provides scientific guidance for the clinical translational research of GEN in the RA treatment.

Keywords: Angiogenesis; Genistein; Rheumatoid arthritis.