Endocrine Abstracts

Background: IGF1 is mainly produced in the liver and it induces beneficial effects on many systems. However, the role of IGF1 on the liver itself is poorly understood, probably due to the fact that healthy hepatocytes barely express IGF1 receptors. Previous works in our group showed that IGF1 supplementation induces beneficial actions in cirrhosis, inducing a relevant histological improvement, reducing fibrosis¹. Based on these data the aim of this work was to inquire into the mechanisms of IGF1 in development of liver architecture using a novel murine model of partial deficiency of IGF1 without other exogenous damage².

Materials and methods: Livers from heterozygous (Igf1^+/−) 5 months old mice (Hz, n=10) were compared to those from homozygous Igf1^+/+ (WT, n=10, same age) by assessing hepatic gene expression (by microarray and further quantitative PCR) of cytoskeleton, cellular junctions, and extracellular matrix proteins. The effect of the replacement therapy with low doses of rhIGF1 (2 μg/100 g Bw per day, for 10 days, s.c.) was evaluated in parallel (group Hz+IGF, n=10, same age). Complementarily, histological studies were performed.

Results: Compared to controls, Hz mice showed a significant alteration of genes encoding proteins of the cytoskeleton and hepatocellular junctions which appear to cause abnormal hepatic architecture, as it was asseverated by histological studies, showing misalignment of hepatocyte cords. An abnormal gene expression of liver extracellular matrix was also observed in Hz mice. IGF1 replacement therapy normalized liver morphology and improved gene expression of many of these factors.

Conclusion: The mere IGF1 deficiency lead to an increase in liver vulnerability by modifying the expression of hepatic genes involved in the morphogenesis of the live and IGF1 replacement therapy normalizes these findings improving the hepatocellular architecture.

1. Tutau F.I. et al. 2009 Liver Int 29 (1) 37-46.

2. Castilla-Cortazar I. et al. 2013 J Physiol Biochem [Epub ahead of print]