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Int. J. Mol. Sci. 2018, 19(9), 2509; https://doi.org/10.3390/ijms19092509

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

1
Department of Pathology and Laboratory Medicine, Kanazawa Medical University, 1-1 Uchinada, Ishikawa 920-0293, Japan
2
Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan
3
Medical Research Institute, Kanazawa Medical University, 1-1 Uchinada, Ishikawa 920-0293, Japan
4
Department of Thoracic Surgery, Kanazawa Medical University, 1-1 Uchinada, Ishikawa 920-0293, Japan
*
Authors to whom correspondence should be addressed.
Received: 1 August 2018 / Revised: 16 August 2018 / Accepted: 21 August 2018 / Published: 24 August 2018
(This article belongs to the Special Issue Liver Damage and Repair)
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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. View Full-Text
Keywords: PRDX4; liver injury; oxidative stress; cholestasis; BDL PRDX4; liver injury; oxidative stress; cholestasis; BDL
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Zhang, J.; Guo, X.; Hamada, T.; Yokoyama, S.; Nakamura, Y.; Zheng, J.; Kurose, N.; Ishigaki, Y.; Uramoto, H.; Tanimoto, A.; Yamada, S. Protective Effects of Peroxiredoxin 4 (PRDX4) on Cholestatic Liver Injury. Int. J. Mol. Sci. 2018, 19, 2509.

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