Hepatocyte integrity depends on c-Jun-controlled proliferation in Schistosoma mansoni infected mice.
Autor: | Härle L; Department of Gastroenterology, Justus Liebig University Giessen, Gaffkystr. 11c, 35392, Giessen, Germany., von Bülow V; Department of Gastroenterology, Justus Liebig University Giessen, Gaffkystr. 11c, 35392, Giessen, Germany., Knedla L; Department of Gastroenterology, Justus Liebig University Giessen, Gaffkystr. 11c, 35392, Giessen, Germany., Stettler F; Department of Gastroenterology, Justus Liebig University Giessen, Gaffkystr. 11c, 35392, Giessen, Germany., Müller H; Department of Gastroenterology, Justus Liebig University Giessen, Gaffkystr. 11c, 35392, Giessen, Germany., Zahner D; Central Laboratory Animal Facility, Justus Liebig University Giessen, 35392, Giessen, Germany., Haeberlein S; Institute of Parasitology, BFS, Justus Liebig University Giessen, 35392, Giessen, Germany., Windhorst A; Institute of Medical Informatics, Justus Liebig University Giessen, 35392, Giessen, Germany., Tschuschner A; Department of Gastroenterology, Justus Liebig University Giessen, Gaffkystr. 11c, 35392, Giessen, Germany., Burg-Roderfeld M; Hochschulen Fresenius GmbH, University of Applied Sciences, 65510, Idstein, Germany., Köhler K; Institute of Veterinary Pathology, Justus Liebig University Giessen, Giessen, Germany., Grevelding CG; Institute of Parasitology, BFS, Justus Liebig University Giessen, 35392, Giessen, Germany., Roeb E; Department of Gastroenterology, Justus Liebig University Giessen, Gaffkystr. 11c, 35392, Giessen, Germany., Roderfeld M; Department of Gastroenterology, Justus Liebig University Giessen, Gaffkystr. 11c, 35392, Giessen, Germany. martin.roderfeld@innere.med.uni-giessen.de. |
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Jazyk: | angličtina |
Zdroj: | Scientific reports [Sci Rep] 2023 Nov 21; Vol. 13 (1), pp. 20390. Date of Electronic Publication: 2023 Nov 21. |
DOI: | 10.1038/s41598-023-47646-z |
Abstrakt: | 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-Jun Δli ) was confirmed by immunohistochemistry and western blotting. Infection with S. mansoni induced elevated aminotransferase-serum levels in c-Jun Δli mice. Of note, hepatic Cyclin D1 expression was induced in infected c-Jun f/f control mice but to a lower extent in c-Jun Δli 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-Jun Δli mice compared to infected c-Jun f/f controls. Enhanced liver damage in c-Jun Δli 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-Jun Δli mice cumulatively led to a loss of the protective potential being responsible for the increased hepatocyte damage and loss of regenerative ability. (© 2023. The Author(s).) |
Databáze: | MEDLINE |
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