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

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机构: [a]Center for Translational Medicine Research and Development, Shen Zhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, Guangdong,518055, China [b]University of Chinese Academy of Sciences, Beijing, 10049, China [c]University of Chinese Academy of Sciences, Shenzhen Hospital, Shenzhen, 518000, China [d]State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science andTechnology, Macau, China [e]Department of Orthopedic, University of Chinese Academy of Sciences Shenzhen Hospital, 518000, Shenzhen, China [f]Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine,Shanghai 200011, China [g]Shenzhen Pingle Orthopaedic Hospital, Guangdong, 518000, China [h]Department of Rheumatology, People's Hospital of Bao'an District, Shenzhen, Guangdong, 518128, China [i]Department of Orthopaedic, The First Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Ji'nan, Shandong, 250000, China [j]School of Dentistry, Cardiff University, Cardiff, Heath Park, CF23 6AL, UK [k]Shenzhen Middle School, Shenzhen, Guangdong, 518001, China [l]Huizhou Second Maternal and Child Health Care Hospital, Huizhou, Guangdong, 516001, China [m]Shenzhen Engineering Research Center for Medical Bioactive Materials, Shenzhen, Guangdong, 518055, China
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关键词: Angiogenesis Genistein Rheumatoid arthritis

摘要:
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.

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大类 | 3 区 医学
小类 | 3 区 骨科
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大类 | 1 区 医学
小类 | 1 区 骨科
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Q1 ORTHOPEDICS
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Q1 ORTHOPEDICS

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第一作者机构: [a]Center for Translational Medicine Research and Development, Shen Zhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, Guangdong,518055, China [b]University of Chinese Academy of Sciences, Beijing, 10049, China [m]Shenzhen Engineering Research Center for Medical Bioactive Materials, Shenzhen, Guangdong, 518055, China
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通讯机构: [a]Center for Translational Medicine Research and Development, Shen Zhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, Guangdong,518055, China [b]University of Chinese Academy of Sciences, Beijing, 10049, China [c]University of Chinese Academy of Sciences, Shenzhen Hospital, Shenzhen, 518000, China [e]Department of Orthopedic, University of Chinese Academy of Sciences Shenzhen Hospital, 518000, Shenzhen, China [f]Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine,Shanghai 200011, China [m]Shenzhen Engineering Research Center for Medical Bioactive Materials, Shenzhen, Guangdong, 518055, China [*1]Center for Translational Medicine Research and Development, Shen Zhen Institute of Advanced Technology, Chinese Academy of Science, 1068 Xueyuan Avenue, Shenzhen, Guangdong, 518055,China [*2]Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China
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