Expression of IGF-I and IGF-binding protein genes in cirrhotic liver.
The liver plays a central role in the IGF-I axis producing the majority of circulating hormone and some of its binding proteins (IGFBPs). Cirrhosis of the liver is characterised by changes in IGF-I and IGFBPs associated with liver fibrosis and regeneration. We have studied steady state levels of mRNA for the genes in the IGF-I axis in normal and cirrhotic 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 IGFBP-3 in cirrhotic patients. Messenger RNA for IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 was detectable by Northern blotting in normal and cirrhotic liver although there was considerable variation in expression. IGFBP-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 hybridisation localised IGFBP-1 to hepatocytes. In cirrhotic liver the regenerating nodules showed expression of IGFBP-1 while there was none in fibrotic tissue. Circulating IGFBP-3 levels were low as measured by RIA and WLB but protease activity was only found in one patient. IGFBP-2 levels, assessed by WLB, were similar to the normal serum pool. Our data show 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 increased protease activity.
Ross
R J
RJ
Department of Medicine, University of Sheffield, UK.
Chew
S L
SL
D'Souza Li
L
L
Yateman
M
M
Rodriguez-Arnao
J
J
Gimson
A
A
Holly
J
J
Camacho-Hubner
C
C
D000293:Adolescent; D000328:Adult; D015152:Blotting, Northern; D015153:Blotting, Western; D002648:Child; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000235:genetics; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008103:Liver Cirrhosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D012038:Regeneration
D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D010447:Peptide Hydrolases