These authors contributed equally to this work.
Endogenous signal transducer and activator of transcription 3 is required for the protection of hepatocytes against warm ischemia/reperfusion injury
Article first published online: 24 SEP 2013
Copyright © 2013 American Association for the Study of Liver Diseases
Volume 19, Issue 10, pages 1078–1087, October 2013
How to Cite
Lou, L. X., Uemura, T., Mani, H., Yang, C., Li, W., Kadry, Z. and Zhang, S. S.-M. (2013), Endogenous signal transducer and activator of transcription 3 is required for the protection of hepatocytes against warm ischemia/reperfusion injury. Liver Transpl, 19: 1078–1087. doi: 10.1002/lt.23693
The authors have no conflicts of interest to declare.
This project was supported by the Pennsylvania Tobacco Settlement Funds.
- Issue published online: 24 SEP 2013
- Article first published online: 24 SEP 2013
- Accepted manuscript online: 9 JUL 2013 02:52AM EST
- Manuscript Accepted: 5 JUN 2013
- Manuscript Received: 18 JAN 2013
- The Pennsylvania Tobacco Settlement Funds
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. Liver Transpl 19:1078–1087, 2013. © 2013 AASLD.