Differential gene expression and functional analysis of pit cells from regenerating rat liver

Xu, Cang‐Bao; Xg, Chen; Cf, Chang; Gp, Wang; Wb, Wang; Lx, Zhang; Qs, Zhu; Wang, L

doi:10.4238/vol10-2gmr1052

Cited by 3 publications

(3 citation statements)

References 22 publications

(19 reference statements)

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“…The most important role of OPN signaling pathway in PCs was to promote inflammation response (Locatelli et al, 2013), cytoskeleton reorganization, and spreading, which was similar to the report of Xu et al (2011c). However, its role was to inhibit apoptosis and promote cell proliferation in HCs (Figure 6), which agreed with the viewpoint of Patouraux et al (2014).…”

Section: Regulatory Roles Of Each Branch Of Opn Signaling Pathway In supporting

confidence: 82%

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

Wang

Chen

et al. 2015

Cell Biology International

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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.

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Section: Regulatory Roles Of Each Branch Of Opn Signaling Pathway In supporting

confidence: 82%

“…essential for hepatic defense response (Xu et al, 2011c). OPN signaling pathway could promote secretion of various cytokines, and then modulate inflammation and immune reaction (Wang and Denhardt, 2008).…”

Section: Regulatory Roles Of Each Branch Of Opn Signaling Pathway In mentioning

confidence: 99%

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

Wang

Chen

et al. 2015

Cell Biology International

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“…According to our data, the proliferation-promoting G-protein/PI3K/Rac pathway in SECs was decreased, whereas the G-protein/PKA/Rap1 pathway increased, and the regulatory effects of the 2 pathways on SEC proliferation are opposed, consistent with a minor role for ERK1/2. Regarding the proliferation dynamics of 3 additional liver immune cells (KCs, PCs, and DCs), as far as we know, DNA replication reaches a peak 48 h post-PH in KCs; for PCs, the peak occurs 24-72 h after PH (Xu et al, 2011), and the timing for DCs is unclear. In this study, the RTK/ PKC/Ras and RTK/Grb2/Ras pathways in KCs were activated during the progressing phase, and these 2 pathways likely contribute to KC repopulation at this time.…”

Section: Discussionmentioning

confidence: 99%

Involvement of ERK1/2 signaling in proliferation of eight liver cell types during hepatic regeneration in rats

Chen¹,

Xu²,

Liu³

2013

Genet. Mol. Res.

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ABSTRACT. It has been well established that ERK1/2 signaling, often subdivided into nine types of pathways, can regulate the hepatocyte proliferative response during liver regeneration. However, the effect of ERK1/2 signaling on the proliferation of other hepatic cell types remains unclear. We isolated and purified 8 liver cell types at 10 time points after 2/3 hepatectomy in adult rats. For each cell type, mRNA expression changes for ERK1/2 signaling-involved genes were monitored up to 168 h, using microarrays. Real-time PCR assays were performed for array data verification. The expression levels of these genes varied considerably between different cell types. Integrating microarray results with gene synergical analysis, at the priming phase, activation of integrin/Grb2/Ras pathway in hepatocytes apparently contributed to G0/G1 transition. Two other pathways, G-protein/EPAC/Rap1 and G-protein/PKA/Rap1, were stimulated in hepatic stellate cells, while RTK/PKC/Ras and RTK/Grb2/Ras were stimulated in Kupffer cells. At the progressive phase, the ERK1/2 pathway is involved in hepatocyte replication; three pathways, namely Ca G-protein/EPAC/Rap1, were found to play roles in biliary epithelial cell proliferation, while RTK/PKC/Ras and RTK/Grb2/Ras were involved in Kupffer cell proliferation, and G-protein/PKC/Ras in pit cell proliferation. At the terminal phase, the promotive effect of the ERK1/2 pathway on replication of hepatocytes, biliary epithelial cells, oval cells, hepatic stellate cells, Kupffer cells, and dendritic cells was considerably reduced, possibly due to their differentiation at the end of regeneration. G-protein/PKC/Ras, integrin/Grb2/Ras and G-protein/ PKA/Rap1 pathways were active in sinusoidal endothelial cells, perhaps to aid in their proliferation. We conclude that ERK1/2 has a signaling role in the regulation of proliferation of 8 cell types during liver regeneration process.

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Human parenchymal and non-parenchymal liver cell isolation, culture and characterization

et al. 2013

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Many reports describing parenchymal liver cell isolation have been published so far. However, recent evidence has clearly demonstrated that non-parenchymal liver cells play an important role in many pathophysiologies of the liver, such as drug-induced liver diseases, inflammation, and the development of liver fibrosis and cirrhosis. In this study, we present an overview of the current methods for isolating and characterizing parenchymal and non-parenchymal liver cells.

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Differential gene expression and functional analysis of pit cells from regenerating rat liver

Cited by 3 publications

References 22 publications

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

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

Involvement of ERK1/2 signaling in proliferation of eight liver cell types during hepatic regeneration in rats

Human parenchymal and non-parenchymal liver cell isolation, culture and characterization

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