Stat3-Atg5 signal axis inducing autophagy to alleviate hepatic ischemia-reperfusion injury
Stat3-Atg5 signal axis inducing autophagy to alleviate hepatic ischemia-reperfusion injury
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DOI：
10.1002/jcb.26516
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发表时间：
2018-04-01
影响因子：
4
通讯作者：
Li, Zhong-dong
中科院分区：
文献类型：
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作者：
Han, Yu-fang;Zhao, Yan-bing;Li, Zhong-dong
在我们的实验中，受损的自噬增加了再灌注期间的肝细胞损伤。通过使用巴弗洛霉素A1阻断自噬或敲除Atg5基因的作用证明了Stat3的抗凋亡作用。在这里，我们集中在信号转导和转录激活因子3（Stat3）在调节自噬，以减轻肝脏IRI的作用。我们发现Stat3在肝脏IRI期间上调，并且与自噬信号通路的激活相关。这增加了Stat3的表达，这与高自噬活性有关，减轻了对IR的肝损伤，体内和体外方法都证明了Stat3的耗尽可以消除这种作用。当Stat3被HO 3867或siStat3抑制时，Atg 5蛋白水平降低。我们的结论是，Stat3似乎发挥了关键作用，在肝脏IRI，通过激活自噬，以减轻肝脏IRI，和Atg 5是需要这个过程。这种新途径的鉴定将Stat3的表达水平与Atg5介导的自噬联系起来，可能为针对肝脏IRI的新型保护性疗法的产生提供新的见解。
In performing our experiment, impaired autophagy increased hepatocellular damage during the reperfusion period. It was demonstrated by the effect of blocking autophagy using bafilomycin A1 or knocking Atg5 gene out reduces the anti-apoptotic effect of Stat3. Here we focus on the role of signal transducer and activator of transcription 3 (Stat3) in regulating autophagy to alleviate hepatic IRI. We found that Stat3 was up-regulated during hepatic IRI and was associated with an activation of the autophagic signaling pathway. This increased Stat3 expression, which was allied with high autophagic activity, alleviated liver damage to IR, an effect which was abrogated by Stat3 epletion as demonstrated in both in vivo and in vitro methods. The levels of Atg5 protein were decreased when Stat3 was inhibited by HO 3867 or siStat3. We conclude that Stat3 appeared to exert a pivotal role in hepatic IRI, by activating autophagy to alleviate hepatic IRI, and Atg5 was required for this process. The identification of this novel pathway, that links expression levels of Stat3 with Atg5-mediated autophagy, may provide new insights for the generation of novel protective therapies directed against hepatic IRI.