Z Gastroenterol 2010; 48 - P2_02
DOI: 10.1055/s-0029-1246382

Impaired liver regeneration in GBA2-deficient mice

ER Almajan 1, R Sandhoff 2, MC Gonzales 1, R Büttner 3, S Weber 4, F Lammert 4, T Sauerbruch 1, Y Yildiz 5
  • 1Department of Internal Medicine I, University of Bonn, Bonn
  • 2Department of Cellular and Molecular Pathology, German Cancer Research Center, Heidelberg
  • 3Department of Pathology, University of Bonn, Bonn
  • 4Abteilung für Innere Medizin II, Uniklinikum Saarland, Homburg
  • 5Medizinische Klinik I, Universität Bonn, Bonn

Beta-glucosidase 2 (GBA2) deficient mice accumulate the naturally occurring glycolipid glucosylceramide (GlcCer) in different tissues, including the liver. Glycolipids are a class of cellular lipids that differ from the regular membrane phospholipids in a remarkable variation in its head group structures. This suggests that glycolipids serve specialized functions in cell signalling, proliferation differentiation and recognition processes, all involved in liver regeneration. Since significant changes in the glycolipid content and distribution have been reported during rat liver regeneration, the present study was performed to evaluate the role of GlcCer in liver regeneration using the two-thirds partial hepatectomy model according to the method of Higgins and Anderson. The GBA2-deficient mice showed during the liver regeneration significantly higher amounts of GlcCer as compared to the control animals. We observed a significantly delay in liver regeneration at 72 hour post hepatectomy in GBA2-deficient mice with a decreased DNA synthesis indicated by 5-bromo-2’-deoxyuridine staining. The IL-6 and TNF-a serum levels in GBA2-deficient mice do not reach the peaks of the control animals and decrease faster to low levels. The phosphorylated signal transducer and activator of transcription 3 (P-STAT3) and the phosphorylated Jun N-terminal kinase (P-JNK) is increased at 0 and 6 hours and again after 120 and 168 hours post hepatectomy.

Conclusion: Glucosylceramide trigger the cytokine-mediated and the growth factor-mediated pathway of liver regeneration.

Literatur: Yildiz Y, Matern H, Thompson B, Allegood JC, Warren RL, Ramirez DM, Hammer RE, et al. Mutation of beta-glucosidase 2 causes glycolipid storage disease and impaired male fertility. J Clin Invest 2006;116:2985-2994. van Meer G, Wolthoorn J, Degroote S. The fate and function of glycosphingolipid glucosylceramide. Philos Trans R Soc Lond B Biol Sci 2003;358:869-873. Riboni L, Ghidoni R, Benevento A, Tettamanti G. Content, pattern and metabolic processing of rat-liver gangliosides during liver regeneration. Eur J Biochem 1990;194:377-382.

IL-6 - STAT-3 - TNF-a - glucosylceramide - partial hepatectomy