Expression profiles uncover the relevance between colony stimulating factor-mediated signaling pathways in liver cells and partial hepatectomy-induced hepatic regeneration

Abstract

ABSTRACT. Colony stimulating factors (CSF) have been considered to modulate liver regeneration (LR) after partial hepatectomy (PH) at the tissue level. However, it remains unclear about precise mechanism of action of CSF in regeneration at the cellular level. Therefore, eight rat liver cell types were isolated by Percoll gradient centrifugation and magnetic beads. CSF-mediated signaling pathway genes were obtained by searching the related pathway databases and their expression profiles in 8 hepatic cell types were measured using rat Genome 230 2.0 Microarray. RT-PCR was performed to assess the reliability of chip results. The result showed a large difference in expression profiles of CSF-mediated signaling pathway genes between different cell types; most genes involved in CSF-mediated signaling pathways were mainly unregulated across liver cell samples. The implication of these genes in LR was analyzed by the bioinformatics and systems biology method. According to chip results and gene synergy, a significant enhancement of the CSF3-mediated Pi3k/Akt pathway at 30-36 h in hepatocytes and at 24 h in biliary epithelial cells post-PH could be associated with active proliferation in these two cell types; the striking decrease in Jak/Stat cascade activity in hepatic stellate cells at 2 and 12 h post-PH or even inactive in dendritric cells during the whole LR implied that proliferation of these two cell types is possibly regulated by other signaling pathways. These data suggest the potential relevance of CSF in liver regeneration at the cellular level.

Podoplanin discriminates distinct stromal cell populations and a novel progenitor subset in the liver

“…Besides TSG-6, DPs were selectively enriched in G-CSF during liver inflammation. Based on genetic analyses, CSF signaling occurs together with liver regeneration and progenitor expansion (2,33) and has been recently identified in human livers (32), stressing its relevance in this process. Notably, G-CSF expression was not exclusively restricted to gp38 ϩ CD133 ϩ cells but could be found in liver parenchymal cells (data not shown).…”