自噬
PI3K/AKT/mTOR通路
关节炎
蛋白激酶B
医学
纤维化
沃特曼宁
癌症研究
药理学
信号转导
细胞生物学
化学
细胞凋亡
内科学
生物
外科
全膝关节置换术
生物化学
作者
Qi Wan,Hui Chen,Guirun Xiong,Rui Jiao,Haibo Liu,Xiaolei Li,Yu Sun,Jingcheng Wang,Lianqi Yan
标识
DOI:10.1016/j.ejphar.2019.04.017
摘要
Intraarticular fibrosis following knee surgery is a troublesome complication and remains a challenging problem for clinicians. Artesunate (ART), a classical anti-malarial drug extracted from the Chinese medicinal herb Artemisia annua L, has been associated with some fibrosis-related diseases. However, its effect and underlying mechanism on knee arthrofibrosis are still obscure. In the present study, we found that ART induced cellular autophagy flux and inhibited cell proliferation in fibroblasts. Intriguingly, genetic depletion of Beclin-1 abolished ART-triggered cellular autophagy and further attenuated the inhibitory effect of ART on fibroblasts proliferation. Moreover, at molecular level, our results demonstrated that ART-induced autophagy activation was associated with the inhibition of mTOR signaling through PI3K/AKT/mTOR pathway and AMPK/mTOR pathway. In vivo, ART treatment triggered autophagy activation and alleviated the severity of surgery-induced knee arthrofibrosis. Taken together, we concluded that ART exhibited anti-proliferation efficacy in fibroblasts and alleviated the severity of knee arthrofibrosis in rabbits by inducing Beclin-1-mediated autophagy via inhibition of mTOR signaling. These findings indicated that ART might be a potential therapeutic agent for preventing the progression of surgery-induced intraarticular fibrosis of knee.
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