Cellular and molecular gastroenterology and hepatology · 2023
Schistosoma mansoni-Induced Oxidative Stress Triggers Hepatocellular Proliferation.
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von Bülow Verena, Schneider Maryam, Dreizler Dorothee, Russ Lena, Baier Anne, Buss Nicola, Lichtenberger Jakob, Härle Lukas, Müller Heike, Tschuschner Annette, Schramm Gabriele, Pons-Kühnemann Jörn, Grevelding Christoph G, Roeb Elke, Roderfeld Martin
Аннотация
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.
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.