Expression of Augmenter of Liver Regeneration in Human Liver Cirrhosis and Carcinoma

Abstract

Aims: Recently, a protein termed “Augmenter of Liver Regeneration“ (ALR) was found to have a specific and beneficial effect on the proliferation of damaged liver tissue. It was proposed that ALR, as a member of hepatotrophic growth factors might act through auto- and paracrince mechanism during liver regernation, but little is known about its expression in normal and diseased human liver. Methods and Results: ALR expression in normal (n=18) and cirrhotic livers (n=25) with various underlying diseases as well as in tissue samples of hepatocellular carcinoma (HCC) (n=9) and cholangiocellular carcinoma (CCC) (n=5) were analyzed by immunohistochemistry and quantitative RT-PCR. Expression analysis of ALR in total protein extracts of human liver by western blotting showed monomeric ALR protein under reducing and higher molecular weight dimeric structures under non reducing conditions. Performing immunohistochemistry cytosolic and perinuclear immunosignals were found in hepatocytes and cholangiocytes in normal, and more intense in cirrhotic or cancerous liver tissue. In non-parenchymal liver-cells no immunostaining was observed except for weak signals in some endothelial cells in normal livers. Quantitative mRNA analysis revealed significantly increased ALR expression in cirrhosis compared to normal liver tissue. In HCC and CCC ALR mRNA expression was also significantly enhanced compared to normal liver tissue, but expression levels did not differ from the matching non-tumorous tissue in the same patient. Conclusions: The expression pattern of increased hepatic ALR under different pathophysiological conditions together with its known hepatotrophic effects indicate an important role of ALR in hepatocellular regeneration in liver cirrhosis as well as in hepatocarcinogenesis and therefore its potential use for clinical diagnosis of development liver cirrhosis and cancer.