ALR expression indicates liver regeneration upon distinct tissue damage

Hepatocellular regeneration requires various factors promoting cellular proliferation. Among them, ALR (augmenter of liver regeneration), was discovered to be highly expressed in vivo under circumstances of liver regeneration and in liver diseases such as cirrhosis and carcinoma. Interestingly, ALR was shown to exhibit its action exclusively on regenerating livers and hepatoma cells. Therefore ALR is an interesting target to analyze liver regeneration. The aim of this study was to investigate the molecular regulation and expression of ALR in murine models of liver damage caused by tissue loss through 70% liver resection, by bile duct ligation, CCl4 intoxication, by fatty liver through a methionine choline deficient diet (MCD) and a high fat diet (lard, cholesterol, Na-cholate) model. ALR mRNA Expression was analyzed by quantitative RT-PCR in liver tissue samples at different time points. ALR mRNA levels were significantly enhanced in liver samples after 2/3 partiel hepatectomy in short (up to 72h) and long term oberservation (12d). Additionally, carbon tetrachloride treatment resulted in a slightly increase of ALR expression within 24 to 72 hours. Bile duct ligation as a model for acute fibrosis displayed intense ALR mRNA levels after 6 weeks. As models for non alcoholic steatohepatits (NASH), MCD and Paigen diet were used representing fatty livers with high and mild fibrotic scores, respectively. In both models liver sample demonstrated high ALR mRNA levels after 3 and 12 weeks with higher expression rates within Paigen mice. In all models a profound inflammation reaction was described and therefore it is likely, that enhanced levels of proflammatory cytokines such as IL-1 are abundant. The latter was shown to activate ALR promoter and ALR expression and might explain our observations. Analysis of ALR expression in different mouse liver disease models might be a useful indicator of an activated process leading to liver regeneration and repair.