Expression profiles uncover the correlation of OPN signaling pathways with rat liver regeneration at cellular level

Abstract Osteopontin (OPN) could participate in the occurrence of multiple liver diseases via promoting inflammation, cell activation, proliferation, and migration. However, the correlation of OPN with liver regeneration (LR) is poorly defined. Previous studies from us and others revealed that OPN was probably involved in the activation and proliferation of various hepatic cell types during LR. In this study, to further investigate the underlined mechanism of OPN in regulating LR, eight hepatic cell types were isolated and purified from rat regenerative livers at 10 time points. The gene expression profiles of above hepatic cells were assayed by Rat Genome 230 2.0 chips, and then IPA software was used to uncover the correlations of gene expression changes with physiological activities. The findings demonstrated that the majority of the OPN pathway‐related genes were up‐regulated in hepatocytes (HCs), pit cells (PCs), oval cells (OCs), and biliary epithelial cells (BECs) but down‐regulated in other four cell types including sinusoidal endothelial cells (SECs), Kupffer cells (KCs), dendritic cells (DCs), and hepatic stellate cells (HSCs). Thereafter, functional enriched analysis by IPA indicated that OPN signaling pathway might promote cell proliferation, activation, migration, and inflammation in HCs, OCs, BECs, and PCs, and slightly boost proliferation and migration of SECs and KCs but inhibit inflammation response and chemotaxis in SECs and KCs and almost all physiological processes in DCs and HSCs. Morever, apoptosis, cell death, and necrosis were remarkably inhibited through JAK/STAT, ERK1/2, and NF‐kB branches in almost every cell type. These above results suggest that OPN signaling pathway is closely related to HCs, OCs, BECs, and PCs but has less regulatory effect on SECs, KCs, HSCs, and DCs during rat LR.