Hepatic insulin-like growth factor receptor is upregulated by activation of the GSK3B-FOXO3 pathway after partial...

Liver regeneration after partial hepatectomy (PH) is a complex and well-elaborated biological process whereby synchronized cell proliferation is induced in response to the loss of liver mass. Insulin-like growth factor 1 (IGF1) signaling, which plays a crucial role in normal growth and development, is involved in the process of liver regeneration. To assess the changes in the levels of serum IGF1 and hepatic IGF1 receptor (IGF1R), we established a mouse model for PH. This also allowed us to further explore the mechanisms that participate in the regulation of liver regeneration. Serum IGF1 dramatically decreased immediately after PH, and was mildly elevated afterwards. This was also confirmed in patients who had undergone PH. Immunohistochemistry and Western blotting showed that hepatic IGF1R expression was elevated after surgery in mice. Hepatosomatic index showed a mild elevation 1 week after surgery and a marked elevation after 3 weeks. Western blotting showed increased levels of forkhead box O3 (FOXO3), but the phosphorylated forms of v-akt murine thymoma viral oncogene homolog 1 (AKT1), glycogen synthase kinase 3 beta (GSK3B) and FOXO3 were all downregulated. Our data show that the GSK3B-FOXO3 pathway is activated after PH, and this may be one of the mechanisms that lead to upregulation of hepatic IGF1R after PH. All these changes after surgery promote liver regeneration.