Curcumin Inhibits Joint Contracture through PTEN Demethylation and Targeting PI3K/Akt/mTOR Pathway in Myofibroblasts from Human Joint Capsule
Curcumin Inhibits Joint Contracture through PTEN Demethylation and Targeting PI3K/Akt/mTOR Pathway in Myofibroblasts from Human Joint Capsule
复制标题
姜黄素通过 PTEN 去甲基化和靶向人关节囊肌成纤维细胞中的 PI3K/Akt/mTOR 通路抑制关节挛缩
DOI：
10.1155/2019/4301238
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发表时间：
2019-08
影响因子：
--
通讯作者：
Wang Kun
中科院分区：
文献类型：
--
作者：
Zhuang Ze;Yu Dongjie;Chen Zheng;Liu Dezhao;Yuan Guohui;Ni Yirong;Sun Linlin;Liu Yuangao;He Ronghan;Wang Kun
关节挛缩症越来越被认为是导致不可逆性关节功能障碍的临床问题。这是关节损伤后的一个病理生理过程，以肌成纤维细胞的激活为标志。目前还没有有效的治疗方法来预防关节痉挛。姜黄素是从姜黄中提取的一种多酚色素，具有抗炎、抗氧化、抗肿瘤等作用。在本研究中，我们证实了姜黄素通过抑制肌成纤维细胞的增殖和迁移而发挥对关节痉挛的保护作用，并呈时间和浓度依赖关系。此外，我们还发现，在体外培养的肌成纤维细胞和患者体内的肌挛缩囊组织中，磷酸酶和张力同源蛋白(PTEN)表达下调。此外，免疫印迹分析显示PTEN的表达水平与纤维化标记物蛋白α-平滑肌细胞肌动蛋白之间呈负相关。甲基化特异性的聚合酶链式反应结果表明，姜黄素能够以类似去甲基化试剂5-氮杂胞苷的方式使PTEN去甲基化，增加PTEN的表达，并进一步抑制磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素信号转导靶点。总之，我们的数据说明了姜黄素抑制关节痉挛的部分机制。这些结果支持这样的假设，即姜黄素可能被潜在地用作治疗关节痉挛的新候选药物。
Joint contracture is increasingly regarded as a clinical problem that leads to irreversible dysfunction of the joint. It is a pathophysiological process following joint injury, which is marked by the activation of myofibroblasts. There is currently no effective treatment for the prevention of joint contracture. Curcumin is a polyphenol pigment extracted from turmeric, which possesses anti-inflammatory, antioxidative, and antitumor properties. In the present study, we demonstrated that curcumin exerts a protective effect against joint contracture via the inhibition of myofibroblast proliferation and migration in a time- and concentration-dependent manner. Moreover, we indicated that phosphatase and tension homolog (PTEN) was downregulated in myofibroblasts in vitro and in the contracture capsule tissues of patients in vivo. Additionally, western blot analysis revealed a negative correlation between the expression levels of PTEN and the fibrosis marker protein alpha smooth muscle cell actin. Methylation-specific PCR results suggested that curcumin was able to demethylate PTEN in a similar manner to the demethylation agent 5-azacytidine, increasing PTEN expression and further inhibiting phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling. In conclusion, our data illustrate part of the mechanism of curcumin inhibition in joint contracture. These results support the hypothesis that curcumin may potentially be used as a novel candidate for the treatment of joint contracture.
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影响因子：
2.9
作者：
Xie J;Lin W;Huang L;Xu N;Xu A;Chen B;Watanabe M;Liu C;Huang P
通讯作者：
Huang P
影响因子：
5.6
作者：
Kendall RT;Feghali-Bostwick CA
通讯作者：
Feghali-Bostwick CA
Lysocardiolipin 酰基转移酶调节 TGF-β 介导的肺成纤维细胞分化。
影响因子：
7.4
作者：
Huang, Long Shuang;Jiang, Peiyue;Natarajan, Viswanathan
通讯作者：
Natarajan, Viswanathan
影响因子：
2.3
作者：
Unterhauser, FN;Bosch, U;Weiler, A
通讯作者：
Weiler, A
影响因子：
3.5
作者：
Zhou, Xiangjun;Zhang, Jie;Wang, Wei
通讯作者：
Wang, Wei