IGF-1 Induces Growth, Survival and Morphological Change of Primary Hepatocytes on a Galactose-bared Polymer through both MAPK and β-catenin Pathways

Cell Structure and Function

Anup Kumer Kundu¹  Shinichi Hirose¹  Toshihiro Akaike¹  Ezharul Hoque Chowdhury¹  Masato Nagaoka¹  Tadashi Sasagawa¹ 

[1] Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology

关键词: IGF-1;    MAPK;    proliferation;    PVLA;    β-catenin;   

DOI  :  10.1247/csf.28.255

学科分类：分子生物学，细胞生物学和基因

来源: Japan Society for Cell Biology

【 摘 要 】

References(34)Cited-By(3)PVLA poly-(N-p-vinylbenzyl-O-β-D-galactopyranosyl-D-gluconamide) is a glycopolymer composed of hydrophilic carbohydrate side chain and hydrophobic styrene polymer. The hydrophilic carbohydrate residue of PVLA can be recognized as a ligand for hepatocytes asialoglycoprotein receptor (ASGP-R), which is abundant on the hepatocyte cell surface. Adhering to the PVLA coated dishes, hepatocytes try to form aggregates that have a long time survival and also cells in these aggregates exhibit better maintenance of specific hepatocyte functions. Stimulation of the cells with IGF-1 in this culture condition results in the formation of lower aggregates. In addition to the morphological influences of IGF-1 to these cells, we have also found that IGF-1 transmits growth stimulatory responses to hepatocytes on PVLA through both mitogen activated protein kinase (MAPK) pathway and β-catenin pathways. The phosphorylation of MAPK can take place within 5 min of stimulation with IGF-1 and within at least 10 ng/ml of IGF-1 concentration. Inhibition of MAPK activation by MEK-1 inhibitor PD98059 reduces IGF-1 induced MAPK phosphorylation, and also IGF-1 stimulated DNA synthesis. Similarly, the use of PI3-K inhibitor LY294002 also inhibits IGF-1 stimulated DNA synthesis. IGF-1 stimulation enhances the migration of β-catenin from the cytoskeleton and cell membrane to the cytoplasm which also is the reason behind formation of spheroids and lower aggregates. IGF-1 stimulation also shows increased translocalization of β-catenin to the nucleus that is essentially important to produce β-catenin responsive effects to the cells. These studies thus suggest that IGF-1 can stimulate the growth and survival of hepatocytes on PVLA through both MAPK and β-catenin signaling pathways, and that the activation of β-catenin signaling pathway produces the morphological changes of IGF-1 induced cells.

【 授权许可】

Unknown