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Protein S Exacerbates Chronic Liver Injury and Fibrosis
- Source :
- The American Journal of Pathology. 188:1195-1203
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Protein S is a vitamin K-dependent glycoprotein produced mainly in the liver with anticoagulant, anti-inflammatory, immune-modulatory, and antiapoptotic properties. Protein S exacerbates acute liver injury by prolonging the survival of liver immune cells. However, the effect of protein S on chronic liver injury and fibrosis is unknown. Here, we investigated whether human protein S can affect chronic liver injury and fibrosis. Liver injury/fibrosis was induced by carbon tetrachloride injection in mice overexpressing human protein S and in wild-type mice. Human protein S transgenic mice receiving carbon tetrachloride showed significantly higher circulating levels of liver transaminases, increased liver expression of inflammatory cytokines, significantly more extended liver fibrosis, and areas with DNA breakage after chronic injury compared with wild-type mice. Wild-type mice infused with exogenous human protein S exhibited exacerbated liver injury and increased number of hepatic stellate cells compared with untreated mice. Human protein S inhibited apoptosis and increased Akt pathway activation in hepatic stellate cells. The antiapoptotic activity of protein S may play a role in chronic liver injury and subsequent liver fibrosis.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Apoptosis
Mice, Transgenic
030204 cardiovascular system & hematology
Protein S
Pathology and Forensic Medicine
Proinflammatory cytokine
End Stage Liver Disease
Mice
03 medical and health sciences
0302 clinical medicine
Immune system
Fibrosis
Internal medicine
Hepatic Stellate Cells
Animals
Medicine
Carbon Tetrachloride
PI3K/AKT/mTOR pathway
Liver injury
biology
business.industry
medicine.disease
030104 developmental biology
Endocrinology
Liver
biology.protein
Hepatic stellate cell
business
Signal Transduction
Subjects
Details
- ISSN :
- 00029440
- Volume :
- 188
- Database :
- OpenAIRE
- Journal :
- The American Journal of Pathology
- Accession number :
- edsair.doi.dedup.....8f0b863c22732070849eef3ffd1243be