Hepatic IGF-1R overexpression combined with the activation of GSK-3β and FOXO3a in the development of liver cirrhosis.

Abstract

AIMS Liver cirrhosis is the common pathological histology manifest among a number of chronic liver diseases and liver cancer. Circulating levels of insulin growth factor-1 (IGF-1) have been recently linked to liver cirrhosis and the development of liver cancer. Herein, we hypothesized that IGF-1R overexpression combining the activation of GSK-3β and FOXO3a were involved in the development of human and murine chronic liver cirrhosis. METHODS Liver samples of patients were screened from the Tissue Bank of the China-Japan Union Hospital of Jilin University. Mice liver fibrosis model was performed using intraperitoneal injection of carbon tetrachloride (CCl4) for 12weeks. Serum IGF-1 levels were detected by enzyme-linked immunosorbent assays (ELISA). Microscopical examination of liver parenchyma was performed using conventional H&E and Masson's staining. Moreover, we investigated the IGF-1 receptor (IGF-1R) signaling pathway at different period after CCl4 administration. RESULTS Serum IGF-1 levels were significantly decreased in patients with liver cirrhosis, which is concomitant with the declined circulating levels of IGF-1 in 8 to 12weeks CCl4-treated mice. Furthermore, the expression of IGF-1R was significantly higher at 12w compared with control group. In addition, activation of the GSK-3β and FOXO3a were activated during the process of murine chronic liver injury. CONCLUSION The present study demonstrates that decreased circulating IGF-1 levels are involved in human and murine chronic liver disease. Interestingly, overexpression of the IGF-1R, and activation of GSK3β and FOXO3a might be the molecular mechanisms underlying the development of liver cirrhosis.

DOI: 10.1016/j.lfs.2016.01.037

Cite this paper

@article{Liu2016HepaticIO, title={Hepatic IGF-1R overexpression combined with the activation of GSK-3β and FOXO3a in the development of liver cirrhosis.}, author={Wentao Liu and Jing Li and Yan Cai and Qiong Wu and Yue Pan and Yang Chen and Yujing Chen and Xiao Zheng and Wei Li and Xuewen Zhang and Changyong E}, journal={Life sciences}, year={2016}, volume={147}, pages={97-102} }