Rhein Inhibits Autophagy in Rat Renal Tubular Cells by Regulation of AMPK/mTOR Signaling.
Rhein Inhibits Autophagy in Rat Renal Tubular Cells by Regulation of AMPK/mTOR Signaling.
复制标题
大黄酸通过调节 AMPK/mTOR 信号传导抑制大鼠肾小管细胞的自噬
DOI：
10.1038/srep43790
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发表时间：
2017-03-02
影响因子：
4.6
通讯作者：
Sun W
中科院分区：
文献类型：
--
作者：
Tu Y;Gu L;Chen D;Wu W;Liu H;Hu H;Wan Y;Sun W
大黄酸及其生物活性成分大黄酸在东亚国家经常用于治疗慢性肾脏疾病（CKD）。然而，潜在的治疗机制仍不清楚。自噬在CKD中起重要作用。然而，在自噬在CKD中的作用以及大黄和大黄酸的治疗方面，仍有一些重要的相关问题尚未解决。我们设计了一系列实验来研究大黄是否可以减少腺嘌呤（Ade）诱导的肾小管损伤大鼠的肾纤维化和自噬，以及大黄酸是否可以影响大鼠肾小管细胞的自噬通路。我们发现，自噬激活伴随着肾纤维化，自噬和肾纤维化都被大黄抑制。此外，我们还观察到大黄酸可以通过调节AMPK依赖的mTOR信号通路中的关键分子，以及Erk和p38 MAPK信号通路来抑制自噬。这些发现可能部分解释了大黄和大黄酸在临床上治疗CKD患者的治疗机制，并进一步提示靶向自噬及其相关信号通路可能为治疗CKD肾纤维化提供新的策略。
Rhubarb and its bioactive component rhein are frequently used for the treatment of chronic kidney diseases (CKD) in eastern Asia countries. However, the potential therapeutic mechanism remains unclear. Autophagy plays an important role in CKD. However, there were some important related issues that remained unresolved in the role of autophagy in CKD and treatment by rhubarb and rhein. We designed a number of experiments to examine whether rhubarb may reduce renal fibrosis and autophagy in rats with adenine (Ade)-induced renal tubular injury, and whether rhein could affect autophagic pathways in rat renal tubular cells. We found that, autophagic activation accompanied with renal fibrosis in rats with Ade-induced renal tubular injury, and both autophagy and renal fibrosis were attenuated by rhubarb. In addition, we observed that rhein could inhibit autophagy through regulating the key molecules in the AMPK-dependent mTOR signaling pathways, as well as the Erk and p38 MAPKs signaling pathways. These findings may partly explain the therapeutic mechanisms of rhubarb and rhein in treating CKD patients in clinic, and further suggest that targeting autophagy and related signaling pathways may provide new strategies for the treatment of renal fibrosis in CKD.