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.

Osteopontin Promotes Macrophage M1 Polarization by Activation of the JAK1/STAT1/HMGB1 Signaling Pathway in Nonalcoholic Fatty Liver Disease

“…39 Moreover, although a study based on mouse microarray has found that OPN was associated with the JAK/STAT1 pathway, that has not been further confirmed. 40 Therefore, it is reasonable to assume that OPN may activate JAK/STAT pathway in NAFLD to promote inflammation and disease progression. In order to verify that assumption, we examined the levels of phosphorylated of JAK1 and STAT1, and found that OPN significantly activated JAK1 and STAT1.…”

Osteopontin - The stirring multifunctional regulatory factor in multisystem aging

“…In a mouse model of partial hepatectomy, OPN knockout significantly delayed liver regeneration. A gene chip analysis showed that OPN was expressed at high levels in hepatocytes, pit cells, oval cells and bile duct epithelial cells during liver regeneration and participated in the proliferation, differentiation and migration of these cells ( 135 ). According to recent studies, OPN levels in the liver tissue of aged mice are decreased.…”

Osteopontin promotes rat hepatocyte proliferation both in vitro and in vivo

“…Our previous studies have revealed that OPN mRNA was up-regulated at multiple time points during 2-72 h in isolated hepatocytes, Kupffer cells, and dendritic cells from rat regenerated livers after partial hepatectomy (PH) [10], and most of the genes involved in OPN-mediated signaling pathways were significantly-changed in rat regenerated livers, and were mainly associated with stress response, cell activation, proliferation, adhesion and migration [11]. In view of the important roles of OPN during LR and the results of our previous studies, we hypothesized that OPN can directly promote rat hepatocyte proliferation.…”