Salvianolic acid B attenuates inflammation and prevent pathologic fibrosis by inhibiting CD36-mediated activation of the PI3K-Akt signaling pathway in frozen shoulder

被引:10
作者
Yan, Yan [1 ]
Zhou, Min [1 ]
Meng, Ke [2 ]
Zhou, Chuanhai [1 ]
Jia, Xiaoyu [3 ]
Li, Xinhao [1 ]
Cui, Dedong [1 ]
Yu, Menglei [1 ]
Tang, Yiyong [2 ]
Li, Ming [1 ]
Zhang, Jinming [3 ]
Wang, Zhuo [1 ]
Hou, Jingyi [1 ]
Yang, Rui [1 ]
机构
[1] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Orthoped, Guangzhou, Peoples R China
[2] Sun Yat Sen Univ, Affiliated Hosp 8, Dept Orthoped, Shenzhen, Peoples R China
[3] Sun Yat Sen Univ, Guangzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
frozen shoulder; fibrosis; CD36; salvianolic acid B; inflammatory cytokines; PI3K-Akt signaling pathway; ADHESIVE CAPSULITIS; CD36; MACROPHAGE; CYTOKINES;
D O I
10.3389/fphar.2023.1230174
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Frozen shoulder (FS) is characterized by pain and limited range of motion (ROM). Inflammation and fibrosis are accepted as main pathologic processes associated with the development of FS. However, the intrinsic mechanisms underlying pathologic fibrosis remain unclear. We aimed to elucidate the key molecules involved in pathologic fibrosis and explore new therapeutic targets for FS. Synovial fibroblasts isolated from patient biopsies were identified using immunofluorescence. Western blotting, RT-qPCR, cell adhesion tests, and would-healing assays were used to evaluate the fibrosis-related functions of synovial fibroblasts. Elevated cluster of differentiation 36 (CD36) expression was detected in FS using Western blotting and immunohistochemistry. Salvianolic acid b (SaB) inhibited CD36, blocking synovial fibroblast-induced inflammation and fibrosis. Our RNA-seq data showed that knocking down CD36 dramatically impaired the capacity of synovial fibroblasts for cell adhesion and that the PI3K-Akt signaling pathway may be crucial to the fibrotic process of FS. By up-regulating CD36 and inhibiting the phosphorylation of Akt, we demonstrated that CD36 promotes pathologic fibrosis by activating the PI3k-Akt pathway. Finally, rats treated with SaB had improved ROM and less collagen fiber deposition than the FS model group.Conclusion: SaB attenuates inflammation and inhibited the CD36-mediated activation of the PI3K-Akt signaling pathway to block pathologic fibrosis of FS in vitro and in vivo models.
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页数:17
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共 51 条
  • [11] The PI3K/AKT/mTOR interactive pathway
    Ersahin, Tulin
    Tuncbag, Nurcan
    Cetin-Atalay, Rengul
    [J]. MOLECULAR BIOSYSTEMS, 2015, 11 (07) : 1946 - 1954
  • [12] JUN promotes hypertrophic skin scarring via CD36 in preclinical in vitro and in vivo models
    Griffin, Michelle F.
    Borrelli, Mimi R.
    Garcia, Julia T.
    Januszyk, Michael
    King, Megan
    Lerbs, Tristan
    Cui, Lu
    Moore, Alessandra L.
    Shen, Abra H.
    Mascharak, Shamik
    Deleon, Nestor M. Diaz
    Adem, Sandeep
    Taylor, Walter L.
    DesJardins-Park, Heather E.
    Gastou, Marc
    Patel, Ronak A.
    Duoto, Bryan A.
    Sokol, Jan
    Wei, Yuning
    Foster, Deshka
    Chen, Kellen
    Wan, Derrick C.
    Gurtner, Geoffrey C.
    Lorenz, Hermann P.
    Chang, Howard Y.
    Wernig, Gerlinde
    Longaker, Michael T.
    [J]. SCIENCE TRANSLATIONAL MEDICINE, 2021, 13 (609)
  • [13] Hepatic fibrosis and cirrhosis:: The (myo)fibroblastic cell subpopulations involved
    Guyot, C
    Lepreux, S
    Combe, C
    Doudnikoff, E
    Bioulac-Sage, P
    Balabaud, C
    Desmoulière, A
    [J]. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2006, 38 (02) : 135 - 151
  • [14] Melatonin Plays a Role as a Mediator of Nocturnal Pain in Patients with Shoulder Disorders
    Ha, Eunyoung
    Lho, Yun-Mee
    Seo, Hyuk-Jun
    Cho, Chul-Hyun
    [J]. JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 2014, 96A (13) : e108(1)
  • [15] Coexistence of fibrotic and chondrogenic process in the capsule of idiopathic frozen shoulders
    Hagiwara, Y.
    Ando, A.
    Onoda, Y.
    Takemura, T.
    Minowa, T.
    Hanagata, N.
    Tsuchiya, M.
    Watanabe, T.
    Chimoto, E.
    Suda, H.
    Takahashi, N.
    Sugaya, H.
    Saijo, Y.
    Itoi, E.
    [J]. OSTEOARTHRITIS AND CARTILAGE, 2012, 20 (03) : 241 - 249
  • [16] The pathology of frozen shoulder
    Hand, G. C. R.
    Athanasou, N. A.
    Matthews, T.
    Carr, A. J.
    [J]. JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME, 2007, 89B (07): : 928 - 932
  • [17] The effect of myofibroblasts and corticosteroid injections in adhesive capsulitis
    Hettrich, Carolyn M.
    DiCarlo, Edward F.
    Faryniarz, Deborah
    Vadasdi, Katherine B.
    Williams, Riley
    Hannafin, Jo A.
    [J]. JOURNAL OF SHOULDER AND ELBOW SURGERY, 2016, 25 (08) : 1274 - 1279
  • [18] The myofibroblast - One function, multiple origins
    Hinz, Boris
    Phan, Sem H.
    Thannickal, Victor J.
    Galli, Andrea
    Bochaton-Piallat, Marie-Luce
    Gabbiani, Giulio
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2007, 170 (06) : 1807 - 1816
  • [19] Endoplasmic reticulum stress-dependent ROS production mediates synovial myofibroblastic differentiation in the immobilization-induced rat knee joint contracture model
    Jiang, Shihai
    He, Ronghan
    Zhu, Lei
    Liang, Tangzhao
    Wang, Zhe
    Lu, Yunxiang
    Ren, Jianhua
    Yi, Xiaoyou
    Xiao, Dahai
    Wang, Kun
    [J]. EXPERIMENTAL CELL RESEARCH, 2018, 369 (02) : 325 - 334
  • [20] Cytogenetic analysis of the pathology of frozen shoulder
    Kabbabe, Benjamin
    Ramkumar, Satish
    Richardson, Martin
    [J]. INTERNATIONAL JOURNAL OF SHOULDER SURGERY, 2010, 4 (03): : 75 - 78