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Use of a Hanging-weight System for Liver Ischemia in Mice

Use of a Hanging-weight System for Liver Ischemia in Mice

Published on: August 7, 2012

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

Yu-Fang Han¹, Yan-Bing Zhao¹, Jun Li¹

¹Second Department of General Surgery, Jiaozuo People's Hospital, Jiaozuo, Henan, China.

Journal of Cellular Biochemistry

|November 17, 2017

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.

Insights

Signal transducer and activator of transcription 3 (Stat3) activates autophagy to reduce liver injury during hepatic ischemia-reperfusion (IRI). Stat3

Area of Science:

Hepatology
Molecular Biology
Cellular Biology

Background:

Hepatic ischemia-reperfusion (IRI) injury is a significant clinical challenge.
Autophagy plays a complex role in cellular injury and survival.
The role of signal transducer and activator of transcription 3 (Stat3) in hepatic IRI remains incompletely understood.

Purpose of the Study:

To investigate the role of Stat3 in regulating autophagy during hepatic IRI.
To elucidate the protective mechanisms of Stat3 against liver injury.

Main Methods:

In vivo and in vitro models of hepatic IRI.
Pharmacological inhibition and genetic knockout of Stat3.
Assessment of autophagy markers, including Atg5.
Evaluation of hepatocellular damage and apoptosis.

Main Results:

Stat3 expression and autophagic activity were upregulated during hepatic IRI.
Increased Stat3 expression alleviated liver damage, an effect dependent on autophagy.
Stat3 inhibition or depletion reduced autophagy and exacerbated liver injury.
Stat3 activation led to increased Atg5 protein levels, essential for the protective effect.

Conclusions:

Stat3 plays a pivotal role in alleviating hepatic IRI by activating autophagy.
Atg5 is required for Stat3-mediated autophagic protection.
This novel Stat3-autophagy pathway offers potential therapeutic targets for hepatic IRI.

Read full analysis

Keywords:

Atg5 Stat3 autophagy hepatic ischemia-reperfusion injury

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