Wogonin inhibits the migration and invasion of fibroblast-like synoviocytes by targeting PI3K/AKT/NF- κ B pathway in rheumatoid arthritis

被引:9
|
作者
Yang, Haixin [1 ]
Liu, Cuizhen [2 ]
Lin, Xiujuan [2 ]
Li, Xing [3 ]
Zeng, Shan [4 ]
Gong, Zhaohui [5 ]
Xu, Qiang [6 ]
Li, Detang [2 ,7 ,8 ]
Li, Nan [1 ]
机构
[1] Jinan Univ, Sch Tradit Chinese Med, Guangzhou 510632, Peoples R China
[2] Guangzhou Univ Chinese Med, Clin Coll 1, Guangzhou 510405, Peoples R China
[3] Southern Med Univ, Affiliated Hosp 3, Dept Rheumatol & Immunol, Guangzhou 510630, Peoples R China
[4] Jinan Univ, Affiliated Hosp 1, Dept Rheumatol, Guangzhou 510632, Peoples R China
[5] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Dept Cardiovasc, Guangzhou 510405, Peoples R China
[6] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Dept Rheumatol, State Key Lab Tradit Chinese Med Syndrome, Guangzhou 510405, Peoples R China
[7] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Dept Pharm, Guangzhou 510405, Peoples R China
[8] Guangdong Clin Res Acad Chinese Med, Guangzhou 510405, Peoples R China
关键词
Rheumatoid arthritis; Wogonin; Migration; Invasion; Fibroblast -like synoviocyte; DOUBLE-BLIND; INFLAMMATION; DIAGNOSIS; THERAPY; INJURY; GENES; GAMMA; MICE;
D O I
10.1016/j.abb.2024.109965
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Rheumatoid arthritis (RA) is currently an autoimmune inflammatory disease with an unclear pathogenesis. Fibroblast-like synoviocytes (FLSs) have tumor-like properties, and their activation and secretion of pro-inflammatory factors are important factors in joint destruction. Wogonin (5,7-dihydroxy-8-methoxyflavone), a natural flavonoid isolated from Scutellaria baicalensis root, has been shown to have significant antiinflammatory, anti-oxidative stress, and anti-tumor effects in a variety of diseases. However, the role of wogonin in RA has not yet been demonstrated. Purpose: To investigate the inhibitory effect of wogonin on the invasive behavior of fibroblast-like synoviocytes and to explore the mechanism of action of wogonin in RA. Methods: CCK-8, EdU, cell migration and invasion, immunofluorescence staining, RT-qPCR, and protein blot analysis were used to study the inhibitory effects of wogonin on migration, invasion, and pro-inflammatory cytokine overexpression in the immortalized rheumatoid synovial cell line MH7A. The therapeutic effects of wogonin were validated in vivo using arthritis scores and histopathological evaluation of collagen-induced arthritis mice. Results: Wogonin inhibited the migration and invasion of MH7A cells, reduced the production of TNF-alpha, IL-1 beta, IL6, MMP-3 and MMP-9, and increased the expression of IL-10. Moreover, wogonin also inhibited the myofibrillar differentiation of MH7A cells, increased the expression of E-cadherin (E-Cad) and decreased the expression of alpha-smooth muscle actin (alpha-SMA). In addition, wogonin treatment effectively ameliorated joint destruction in CIA mice. Further molecular mechanism studies showed that wogonin treatment significantly inhibited the activation of PI3K/AKT/NF-kappa B signaling pathway in TNF-alpha-induced arthritic FLSs. Conclusion: Wogonin effectively inhibits migration, invasion and pro-inflammatory cytokine production of RA fibroblast-like synoviocytes through the PI3K/AKT/NF-kappa B pathway, and thus wogonin, as a natural flavonoid, has great potential for treating RA.
引用
收藏
页数:15
相关论文
共 50 条
  • [21] uPAR promotes tumor-like biologic behaviors of fibroblast-like synoviocytes through PI3K/Akt signaling pathway in patients with rheumatoid arthritis
    Yan Liu
    Yun Feng Pan
    You-qiu Xue
    Lin-kai Fang
    Xing-hua Guo
    Xin Guo
    Meng Liu
    Bi-yao Mo
    Meng-ru Yang
    Fang Liu
    Yun-ting Wu
    Nancy Olsen
    Song Guo Zheng
    Cellular & Molecular Immunology, 2018, 15 : 171 - 181
  • [22] uPAR promotes tumor-like biologic behaviors of fibroblast-like synoviocytes through PI3K/Akt signaling pathway in patients with rheumatoid arthritis
    Liu, Yan
    Pan, Yun Feng
    Xue, You-qiu
    Fang, Lin-kai
    Guo, Xing-hua
    Guo, Xin
    Liu, Meng
    Mo, Bi-yao
    Yang, Meng-ru
    Liu, Fang
    Wu, Yun-ting
    Olsen, Nancy
    Zheng, Song Guo
    CELLULAR & MOLECULAR IMMUNOLOGY, 2018, 15 (02) : 171 - 181
  • [23] uPAR Promotes Tumor-like Biologic Role of Fibroblast-like Synoviocytes through PI3K/Akt Signaling Pathway in Patients with Rheumatoid Arthritis
    Liu, Yan
    Pan, Yunfeng
    Zheng, Song Guo
    ARTHRITIS & RHEUMATOLOGY, 2016, 68
  • [24] Gastrodia elata attenuates inflammatory response by inhibiting the NF-κB pathway in rheumatoid arthritis fibroblast-like synoviocytes
    Li, Yu
    Wang, Li-min
    Xu, Jian-zhong
    Tian, Ke
    Gu, Chen-xi
    Li, Zhi-fu
    BIOMEDICINE & PHARMACOTHERAPY, 2017, 85 : 177 - 181
  • [25] Effects of TNF-α on autophagy of rheumatoid arthritis fibroblast-like synoviocytes and regulation of the NF-κB signaling pathway
    Wang, Yu
    Gao, Wei
    IMMUNOBIOLOGY, 2021, 226 (02)
  • [26] Correction to: Sam68 Promotes Invasion, Migration, and Proliferation of Fibroblast-like Synoviocytes by Enhancing the NF-κB/P65 Pathway in Rheumatoid Arthritis
    Weiwei Sun
    Rongqing Qin
    Rui Wang
    Dazhi Ding
    Zhaohui Yu
    Yuxi Liu
    Ruilong Hong
    Zhen Cheng
    Youhua Wang
    Inflammation, 2019, 42 : 763 - 763
  • [27] Galangin protects human rheumatoid arthritis fibroblast-like synoviocytes via suppression of the NF-κB/NLRP3 pathway
    Fu, Qiang
    Gao, Yuzhong
    Zhao, Hui
    Wang, Zaijun
    Wang, Jian
    MOLECULAR MEDICINE REPORTS, 2018, 18 (04) : 3619 - 3624
  • [28] MiR-26a-5p enhances cells proliferation, invasion, and apoptosis resistance of fibroblast-like synoviocytes in rheumatoid arthritis by regulating PTEN/PI3K/AKT pathway
    Huang, Zhengping
    Xing, Shan
    Liu, Meng
    Deng, Weiming
    Wang, Yunqing
    Huang, Zhixiang
    Huang, Yukai
    Huang, Xuechan
    Wu, Chiwei
    Guo, Xin
    Pan, Xia
    Jiang, Jiawei
    Feng, Fan
    Li, Tianwang
    BIOSCIENCE REPORTS, 2019, 39
  • [29] Triptolide inhibits the migration and invasion of rheumatoid fibroblast-like synoviocytes by blocking the activation of the JNK MAPK pathway
    Yang, Yanlong
    Ye, Yujin
    Qiu, Qian
    Xiao, Youjun
    Huang, Mingcheng
    Shi, Maohua
    Liang, Liuqin
    Yang, Xiuyan
    Xu, Hanshi
    INTERNATIONAL IMMUNOPHARMACOLOGY, 2016, 41 : 8 - 16
  • [30] Imperatorin Inhibits Proliferation, Migration, and Inflammation via Blocking the NF-?B and MAPK Pathways in Rheumatoid Fibroblast-like Synoviocytes
    Lin, Wei
    Chen, Gang
    Mao, Yuhang
    Ma, Xuemei
    Zhou, Junnan
    Yu, Xiaolu
    Wang, Chaoliang
    Liu, Mei
    ACS OMEGA, 2022, 7 (34): : 29868 - 29876