Stat3‐Atg5 signal axis inducing autophagy to alleviate hepatic ischemia‐reperfusion injury

ABSTRACT 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 sig...

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Published in:Journal of cellular biochemistry 2018-04, Vol.119 (4), p.3440-3450
Main Authors: Han, Yu‐fang, Zhao, Yan‐bing, Li, Jun, Li, Li, Li, Yong‐gan, Li, Shi‐peng, Li, Zhong‐dong
Format: Article
Language:English
Subjects:
Apoptosis
Atg5
Autophagy
hepatic ischemia‐reperfusion injury
In vitro methods and tests
In vivo methods and tests
Ischemia
Liver
Phagocytosis
Reperfusion
Signal transduction
Signaling
Stat3
Stat3 protein
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Summary:ABSTRACT 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. We conclude that Stat3 appeared to exert a pivotal role in hepatic IRI, by activating autophagy to alleviate hepatic ischemia‐reperfusion injury, and Atg5 was required for this process. The identification of this novel pathway, which links expression levels of Stat3 with Atg5‐mediated autophagy, may provide new insights for the generation of novel protective therapies directed against hepatic IRI.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.26516