Hepatocyte integrity depends on c-Jun-controlled proliferation in Schistosoma mansoni infected mice.
Sci Rep
; 13(1): 20390, 2023 11 21.
Article
in En
| MEDLINE
| ID: mdl-37990129
ABSTRACT
Schistosomiasis is a parasitic disease affecting more than 250 million people worldwide. The transcription factor c-Jun, which is induced in S. mansoni infection-associated liver disease, can promote hepatocyte survival but can also trigger hepatocellular carcinogenesis. We aimed to analyze the hepatic role of c-Jun following S. mansoni infection. We adopted a hepatocyte-specific c-Jun knockout mouse model (Alb-Cre/c-Jun loxP) and analyzed liver tissue and serum samples by quantitative real-time PCR array, western blotting, immunohistochemistry, hydroxyproline quantification, and functional analyses. Hepatocyte-specific c-Jun knockout (c-JunΔli) was confirmed by immunohistochemistry and western blotting. Infection with S. mansoni induced elevated aminotransferase-serum levels in c-JunΔli mice. Of note, hepatic Cyclin D1 expression was induced in infected c-Junf/f control mice but to a lower extent in c-JunΔli mice. S. mansoni soluble egg antigen-induced proliferation in a human hepatoma cell line was diminished by inhibition of c-Jun signaling. Markers for apoptosis, oxidative stress, ER stress, inflammation, autophagy, DNA-damage, and fibrosis were not altered in S. mansoni infected c-JunΔli mice compared to infected c-Junf/f controls. Enhanced liver damage in c-JunΔli mice suggested a protective role of c-Jun. A reduced Cyclin D1 expression and reduced hepatic regeneration could be the reason. In addition, it seems likely that the trends in pathological changes in c-JunΔli mice cumulatively led to a loss of the protective potential being responsible for the increased hepatocyte damage and loss of regenerative ability.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Schistosoma mansoni
/
Schistosomiasis mansoni
Limits:
Animals
/
Humans
Language:
En
Journal:
Sci Rep
Year:
2023
Document type:
Article
Affiliation country:
Alemania