Schistosoma mansoni-Induced Oxidative Stress Triggers Hepatocellular Proliferation.
Cell Mol Gastroenterol Hepatol
; 17(1): 107-117, 2024.
Article
em En
| MEDLINE
| ID: mdl-37696392
ABSTRACT
BACKGROUND & AIMS:
Schistosomiasis is one of the most prominent parasite-induced infectious diseases, affecting more than 250 million people. Schistosoma mansoni causes metabolic exhaustion and a strong redox imbalance in the liver, causing parenchymal damage, and may predispose for cancer. We investigated whether oxidative stress provokes hepatocellular proliferation upon S. mansoni infection.METHODS:
The cell cycle, replication stress response, and proliferation were analyzed on transcriptional and protein levels in the livers of S. mansoni-infected hamsters and by mechanistic gain- and loss-of-function experiments in human hepatoma cells. Major results were validated in human biopsy specimens of S. mansoni-infected patients.RESULTS:
S. mansoni infection induced licensing factors of DNA replication and cell-cycle checkpoint cyclins in parallel with a DNA damage response in hamster hepatocytes. Moreover, even unisexual infection without egg effects, as a reflection of a chronic inflammatory process, resulted in a moderate activation of several cell-cycle markers. S. mansoni soluble egg antigens induced proliferation of human hepatoma cells that could be abolished by reduced glutathione.CONCLUSIONS:
Our data suggest that hepatocellular proliferation is triggered by S. mansoni egg-induced oxidative stress.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esquistossomose mansoni
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Carcinoma Hepatocelular
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Neoplasias Hepáticas
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article