Granulocyte–Colony Stimulating Factor Promotes Liver Repair and Induces Oval Cell Migration and Proliferation in Rats

Abstract

Background & Aims-Hepatic regeneration is a heterogeneous phenomenon involving several cell populations. Oval cells are considered liver stem cells, a portion of which derive from bone marrow (BM). Recent studies have shown that granulocyte-colony stimulating factor (G-CSF) may be effective in facilitating liver repair. However, it remains unclear if G-CSF acts by mobilizing BM cells, or if it acts locally within the liver microenvironment to facilitate the endogenous restoration program. In the present study, we assessed the involvement of G-CSF during oval cell activation.

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

“…What needs to be mentioned is that in Kupffer cells, CSF-mediated signaling pathways including Ras/Raf/Mapk, Pi3k/Akt and Jak/Stat became inactive during the whole LR. According to previous studies, CSF could improve liver repair and restoration, implicating the relative active signal pathway triggered by them (Piscaglia et al, 2007). However, the difference between our results and those of other studies suggests the possibility that the inactive CSF-mediated signaling pathways during LR may be try to prevent the regenerating liver from inflammatory injury caused by CSF, or this difference is related to the difference between tissue-level studies and cell-level studies.…”

“…As previously stated, the postoperative administration of CSF1, 2 or 3 promotes the proliferation of hepatic cells by inducing intracellular cascades, thus contributing to liver regeneration (Kaushansky, 2006;Akagawa et al, 2006;Piscaglia et al, 2007). To clarify how CSF impact the regeneration process at the cellular level, we performed high throughput analysis to measure expression profiles of CSF-mediated signaling pathway genes in eight hepatic cell types following PH.…”

“…Recently, some researchers have indicated that the above biological processes are orchestrated by various cytokines, among which colony stimulating factors (CSF) are considered to play an important role in directly enhancing oval cell activation and promoting migration of extrahepatic progenitors into the liver (Piscaglia et al, 2007). CSF is defined as a group of pleiotropic glycoproteins, mainly composed of macrophage-CSF (M-CSF or CSF1), granulocyte-macrophage-CSF (GM-CSF or CSF2), and granulocyte-CSF (G-CSF or CSF3) (Kaushansky, 2006).…”

“…Recently, a study by Meng et al (2012) suggested that the altered expression of GM-CSF after PH can contribute to biliary remodeling after transplantation or partial hepatectomy by functional deregulation of the activity of key signaling intermediates involved in cell expansion and differentiation. Piscaglia et al (2007) showed that G-CSF facilitates 2AAF/PH-induced hepatic regeneration in rats by promoting migration and proliferation of endogenous oval cells. In a study conducted by Kang et al (2008), G-GSF showed an inhibitory effect on hepatocyte apoptosis by probably upregulating Bcl2 and reducing caspase 3 expression.…”

Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly

“…Transplanted oval cells can make a modest (∼2% after 1 month, falling to 0.4% at 6 months) contribution to the hepatocyte population in the CCl 4 -damaged mouse liver [92]. The progenitor response can be manipulated in vivo; in the 2-AAF/PH model the oval cell reaction can be significantly boosted by G-CSF [93], and a small study of patients with alcoholic steatohepatitis found that 5 days of G-CSF treatment resulted in a four-fold increase in proliferating HPCs [94].…”