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Protective Effects of Peroxiredoxin 4 (PRDX4) on Cholestatic Liver Injury

Authors :
Seiya Yokoyama
Taiji Hamada
Sohsuke Yamada
Jianbo Zheng
Hidetaka Uramoto
Yasuhito Ishigaki
Yuka Nakamura
Akihide Tanimoto
Jing Zhang
Xin Guo
Nozomu Kurose
Source :
International Journal of Molecular Sciences, Volume 19, Issue 9, International Journal of Molecular Sciences, Vol 19, Iss 9, p 2509 (2018)
Publication Year :
2018
Publisher :
MDPI AG, 2018.

Abstract

Accumulating evidence indicates that oxidative stress plays a critical role in initiating the progression of inflammatory and fibrotic liver diseases, including cholestatic hepatitis. Peroxiredoxin 4 (PRDX4) is a secretory antioxidase that protects against oxidative damage by scavenging reactive oxygen species (ROS) in both the intracellular compartments and extracellular space. In this study, we examined the in vivo net effects of PRDX4 overexpression in a murine model of cholestasis. To induce cholestatic liver injury, we subjected C57BL/6J wild-type (WT) or human PRDX4 (hPRDX4) transgenic (Tg) mice to sham or bile duct ligation (BDL) surgery for seven days. Our results showed that the liver necrosis area was significantly suppressed in Tg BDL mice with a reduction in the severity of liver injuries. Furthermore, PRDX4 overexpression markedly reduced local and systemic oxidative stress generated by BDL. In addition, suppression of inflammatory cell infiltration, reduced proliferation of hepatocytes and intrahepatic bile ducts, and less fibrosis were also found in the liver of Tg BDL mice, along with a reduced mortality rate after BDL surgery. Interestingly, the composition of the hepatic bile acids (BAs) was more beneficial for Tg BDL mice than for WT BDL mice, suggesting that PRDX4 overexpression may affect BA metabolism during cholestasis. These features indicate that PRDX4 plays an important role in protecting against liver injury following BDL and might be a promising therapeutic modality for cholestatic diseases.

Details

ISSN :
14220067
Volume :
19
Database :
OpenAIRE
Journal :
International Journal of Molecular Sciences
Accession number :
edsair.doi.dedup.....4ca80c253173f2a8789231be8d028181