Salvianolic acid B attenuates inflammation and prevent pathologic fibrosis by inhibiting CD36-mediated activation of the PI3K-Akt signaling pathway in frozen shoulder.
Salvianolic acid B attenuates inflammation and prevent pathologic fibrosis by inhibiting CD36-mediated activation of the PI3K-Akt signaling pathway in frozen shoulder.
复制标题
丹酚酸B通过抑制CD36介导的PI3K-Akt信号通路的激活来减轻炎症和防止病理纤维化。
DOI：
10.3389/fphar.2023.1230174
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发表时间：
2023
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
冻结肩(FS)的特征是疼痛和活动范围受限(ROM)。炎症和纤维化被认为是FS发生发展的主要病理过程。然而，病理性纤维化的内在机制仍不清楚。我们的目标是阐明与病理纤维化相关的关键分子，并探索FS的新治疗靶点。用免疫荧光法鉴定从患者活检组织中分离的滑膜成纤维细胞。采用Western blotting、RT-qPCR、细胞黏附试验和愈合能力试验评价滑膜成纤维细胞的纤维化相关功能。免疫组织化学和Western blotting检测到分化簇36(CD36)在FS中的表达升高。丹酚酸b(SAB)抑制CD36，阻断滑膜成纤维细胞诱导的炎症和纤维化。我们的RNA-seq数据显示，敲除CD36显著削弱了滑膜成纤维细胞的细胞黏附能力，PI3K-Akt信号通路可能在FS的纤维化过程中起关键作用。通过上调CD36和抑制Akt的磷酸化，我们证明CD36通过激活PI3K-Akt通路促进病理纤维化。最后，与FS模型组相比，SAB治疗组大鼠的活动度有所改善，胶原纤维沉积较少。结论：SAB具有抗炎作用，抑制CD36介导的PI3K-Akt信号通路的激活，从而阻断FS的体内外病理纤维化。
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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DOI：
10.1073/pnas.2102715118
发表时间：
2021-09-28
影响因子：
11.1
作者：
Akbar M;Crowe LAN;McLean M;Garcia-Melchor E;MacDonald L;Carter K;Fazzi UG;Martin D;Arthur A;Reilly JH;McInnes IB;Millar NL
通讯作者：
Millar NL
DOI：
10.1016/j.biocel.2005.08.021
发表时间：
2006-02-01
影响因子：
4
作者：
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通讯作者：
Desmoulière, A
影响因子：
3
作者：
Hettrich, Carolyn M.;DiCarlo, Edward F.;Hannafin, Jo A.
通讯作者：
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影响因子：
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作者：
Jiang, Shihai;He, Ronghan;Wang, Kun
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影响因子：
6
作者：
Lin, Hung-Yu;Wang, Feng-Sheng;Huang, Ying-Hsien
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