Abstract
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. The expression of sterol regulatory element-binding protein 2 (SREBP-2) is an important factor in the pathogenesis of fatty livers. To examine the ability of regeneration of fatty livers, 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 select and characterize tissue specimens of patients undergoing surgical liver resection regarding the correlation of 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 Brunt et al. 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=33) 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 ability of fatty livers is increased.
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