Endogenous signal transducer and activator of transcription 3 is required for the protection of hepatocytes against warm ischemia/reperfusion injury

Lucy Xi Lou, Tadahiro Uemura, Haresh Mani, Chen Yang, Weiyi Li, Zakiyah Kadry, Samuel Shao Min Zhang

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Warm ischemia/reperfusion (I/R) is a common clinical problem during liver transplantation and liver resection. Warm ischemia also occurs during trauma and shock. However, there is still no safe and promising strategy for protecting the liver from I/R injury. Signal transducer and activator of transcription 3 (STAT3) is a major immediate response molecule for protecting cell survival. In this study, we first confirmed that a pharmacological STAT3 inhibitor, (E)-2-cyano-3-(3,4-dihydrophenyl)-N-(phenylmethyl)-2-propenamide (AG490), significantly reduced the survival of HepG2 cells, regardless of the serum condition. Furthermore, we created hepatocyte-specific STAT3-deficient mice with the cyclization recombination-locus of X-over P1 (Cre-LoxP) system to study the mechanisms of STAT3 in liver I/R injury. We found that the alanine aminotransferase level was significantly higher in hepatocyte-specific STAT3-deficient mice versus wild-type (WT) mice in a 70% liver I/R injury model. A histopathological examination showed that hepatocyte-specific STAT3-deficient mice suffered more severe damage than WT mice despite similar numbers of polymorphonuclear neutrophils in the 2 groups. These results indicate that endogenous STAT3 signaling in hepatocytes is required for protection of the liver in vitro and in vivo against warm I/R injury. In conclusion, endogenous STAT3 plays an important role in protecting the liver against I/R injury, and STAT3-targeting therapy could be a therapeutic approach to combating liver I/R injury. © 2013 AASLD.

Original languageEnglish (US)
Pages (from-to)1078-1087
Number of pages10
JournalLiver Transplantation
Volume19
Issue number10
DOIs
StatePublished - Oct 2013

All Science Journal Classification (ASJC) codes

  • Surgery
  • Hepatology
  • Transplantation

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