Schistosoma mansoni-Induced Oxidative Stress Triggers Hepatocellular Proliferation.
Cell Cycle
DNA Stress Response
Parasite
Replication Licensing
Journal
Cellular and molecular gastroenterology and hepatology
ISSN: 2352-345X
Titre abrégé: Cell Mol Gastroenterol Hepatol
Pays: United States
ID NLM: 101648302
Informations de publication
Date de publication:
2024
2024
Historique:
received:
16
05
2023
revised:
31
08
2023
accepted:
31
08
2023
medline:
19
12
2023
pubmed:
12
9
2023
entrez:
11
9
2023
Statut:
ppublish
Résumé
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. 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. 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. Our data suggest that hepatocellular proliferation is triggered by S. mansoni egg-induced oxidative stress.
Sections du résumé
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.
Identifiants
pubmed: 37696392
pii: S2352-345X(23)00162-5
doi: 10.1016/j.jcmgh.2023.08.014
pmc: PMC10665951
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
107-117Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.