Metabolic reprogramming of HBsAg-positive hepatocytes after stimulation with Schistosoma mansoni egg antigens

Introduction: Schistosomiasis is a parasitic tropical disease caused by trematodes, affecting over 250 million people worldwide. S. mansoni eggs induce inflammation, granuloma formation and portal hypertension. In endemic regions, co-infections of S. mansoni with hepatitis B virus (HBV) occur frequently. Individuals chronically infected with HBV and S. mansoni exhibit a more severe course of illness and greater liver damage. The effect of co-infection on hepatocellular metabolism remains unclear. Our goal was to characterize hepatocellular carbohydrate metabolism in a cell culture model for co-infection with the use of HBV surface proteins (HBsAg) and Schistosoma mansoni egg antigens.

Methods: Human hepatoma cells (HepG2) and primary mouse hepatocytes were transfected with HBsAg and/or stimulated with purified soluble egg antigens (SEA) obtained from infected hamsters. Metabolism and transcription factors were analyzed using Western blotting, viability assay, immunohistochemistry and a glycogen assay. Group differences were evaluated using one-way ANOVA (p<0.05).

Results: A higher activation of glucokinase (GK), pyruvate kinase 1 (PKM1), glucose-6-phosphate dehydrogenase (G6PDH), and lactate dehydrogenase (LDH) was observed in the S. mansoni+HBsAg groups. Furthermore, the transcription factor and proto-oncogene c-Jun was induced by the individual agents and particularly in the double-stimulated group compared to the controls. The absolute amount of hepatocellular glycogen remained unchanged.

Conclusion: In our model, we demonstrate an increase in cellular stress, as well as an induction of glucose metabolism. The enhanced fermentation of pyruvate to lactate suggests a metabolic reprogramming of hepatocytes to a &quot;Warburg-like glycolysis.&quot; This form of ATP production is associated with malignant

Publication History

Article published online:
20 January 2025