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Protective Effects of Peroxiredoxin 4 (PRDX4) on Cholestatic Liver Injury
- 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.
- Subjects :
- Male
0301 basic medicine
Gene Expression
medicine.disease_cause
lcsh:Chemistry
Mice
0302 clinical medicine
Fibrosis
oxidative stress
lcsh:QH301-705.5
Spectroscopy
Liver injury
chemistry.chemical_classification
Liver Diseases
General Medicine
Prognosis
Computer Science Applications
030211 gastroenterology & hepatology
Disease Susceptibility
Intracellular
liver injury
medicine.medical_specialty
BDL
Intrahepatic bile ducts
Mice, Transgenic
Models, Biological
digestive system
Article
PRDX4
Catalysis
Bile Acids and Salts
Inorganic Chemistry
03 medical and health sciences
Cholestasis
Internal medicine
medicine
Extracellular
Animals
Humans
Physical and Theoretical Chemistry
Molecular Biology
Reactive oxygen species
Organic Chemistry
Peroxiredoxins
medicine.disease
digestive system diseases
Disease Models, Animal
030104 developmental biology
Endocrinology
lcsh:Biology (General)
lcsh:QD1-999
chemistry
Reactive Oxygen Species
cholestasis
Biomarkers
Oxidative stress
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....4ca80c253173f2a8789231be8d028181