Major HGF-mediated regenerative pathways are similarly affected in human and canine cirrhosis

Canine specific mRNA expression of the regenerative hepatocyte growth factor (HGF) signaling pathway and relevant down-stream pathways were measured by semi-quantitative PCR and Western blot (STAT3, PKB, ERK1/2, and p38-MAPK). In all canine groups, levels of c-MET mRNA (proto-oncogenic receptor for HGF) were significantly decreased (p < 0.05). Surprisingly, ERK1/2 and p38-MAPK were increased in CH and LDH. In the human liver samples Western blotting indicated a high homology of down-stream pathways between different etiologies (hALC and hHC). Similarly activated pathways were found in CIRR, hALC, and hHC.In canine hepatitis and cirrhosis the major regenerative downstream pathways were activated. Signaling pathways are similarly activated in human cirrhotic liver samples, irrespective of the differences in etiology in the human samples (alcohol abuse and HCV-infection). Therefore, canine hepatitis and cirrhosis could be an important clinical model to evaluate novel interventions prior to human clinical trials.Chronic hepatitis (CH) and end-stage cirrhosis (CIRR) are an increasing medical problem, affecting over 5% of the world population [1,2]. The best-studied animal model for these liver diseases is tetracarbon-induced fibrotic liver diseases inflicted in rats [3]. Many more models have been devised to mimic liver diseases in man; the time-course of the development however, is not always comparable to the human situation [4-8]. Furthermore, the variability in the affected human population regarding, sex, age, social factors, eating- and drinking behavior, body weight etc. is not fully covered in standardized laboratory conditions.Dogs have liver diseases which are clinically highly comparable with the human counterparts and both species have a high resemblance at the genetic level [9,10]. In contrast to rodent models, hepatitis in these dogs is not deliberately induced. Previous studies already showed a high resemblance between man and dogs in the formation of fibr