Überexpression des Regenerationsfaktors Augmenter of Liver Regeneration (ALR) in humanen Gewebeproben von Fettlebern

Abstract

Neoadjuvant therapy in the treatment of liver metastases often causes fatty degeneration of the liver. So far it is unclear if liver resections in patients with a fatty liver lower the ability for regeneration. The expression of sterol regulatory element-binding protein 2 (SREBP-2) is an important factor in the pathogenesis of fatty livers. Nonalcoholic steatohepatitis (NASH) is a frequently recognized disease which is associated with obesity, insulin resistance and type 2 diabetes mellitus. Despite its frequent contribution, not much is known about the molecular mechanisms involved in NASH genesis. To examine the relation of fatty livers and the ability for regeneration, a RNA data base of specimens and corresponding RNA samples derived from patients with clinical and pathological proven NASH was set up and characterized. Aim of this study was to investigate the correlation between expression patterns of regeneration and lipometabolism. Donors were selected according to body mass index (BMI), alcohol intake and histological features. Patients with excessive alcohol intake, positive serology for hepatitis B, C or a BMI smaller than 30 were excluded from this study. Grading (necroinflammatory activity) and staging (extent of fibrosis) of NASH was done according to severity of fatty degeneration. After RNA isolation and cDNA synthesis, samples were analyzed by real-time PCR. The expression patterns of SREBP-2 and augmenter of liver regeneration (ALR), a growth factor that is upregulated in regenerating liver tissue, were detected in NASH specimens and compared to normal controls. The analysis of the clinical data of NASH (n = 24) and control samples (n = 10) showed an equal distribution in age, medication and previous illnesses. The expression levels of SREBP-2 and ALR were significantly higher in NASH, increasing according to fatty degeneration grade, compared to normal controls. On the basis of the established and characterized RNA data base, a correlation between expression levels of SREBP-2 and ALR was shown in human NASH specimens. Our results indicate that regeneration mechanisms in fatty livers are increased. So far it is not known if regeneration capacity after liver resection is deteriorated in NASH.