EXPRESSION OF ICF-I AND ICF-BINDING PROTEIN GENES IN CIRRHOTIC LIVER

The liver plays a central role in the IGF-I axis producing the majorit y of circulating hormone and some of its binding proteins (IGFBPs). Ci rrhosis of the liver is characterised by changes in IGF-I and IGFBPs a ssociated with liver fibrosis and regeneration. We have studied steady state levels of mRNA for the genes in the IGF-I axis in normal and ci rrhotic human liver, localised the most highly expressed gene, IGFBP-1 , and measured circulating IGFBP-3 by radioimmunoassay (RIA), IGFBP-2 and IGFBP-3 by Western ligand blot (WLB), and protease activity for IG FBP-3 in cirrhotic patients. Messenger RNA for IGF-I, IGFBP-1, IGFBP-2 , and IGFBP-3 was detectable by Northern blotting in normal and cirrho tic liver although there was considerable variation in expression. IGF BP-2 and IGFBP-3 tended to be more highly expressed in cirrhotic liver and IGFBP-1 was more highly expressed in normal liver, although there were no significant differences. In normal liver, in situ hybridisati on localised IGFBP-1 to hepatocytes. In cirrhotic liver the regenerati ng nodules showed expression of IGFBP-1 while there was none in fibrot ic tissue. Circulating IGFBP-3 levels were low as measured by RIA and WLB but protease activity was only found in one patient. IGFBP-2 level s, assessed by WLB, were similar to the normal serum pool. Our data sh ow that key mRNAs involved in the IGF-I axis continue to be expressed in cirrhotic liver despite end stage liver disease. The low levels of IGFBP-3 do not appear to be due to reduced gene transcription or incre ased protease activity.