Hepatic gene induction in murine bone marrow after hepatectomy

Abstract

Bone marrow cells are highly plastic and differentiate into various cell types, including hepatocytes. To explore the mechanisms underlying these processes, we focused on the initial responses of bone marrow to hepatectomy, using a mouse model. To evaluate hepatic differentiation in bone marrow cells we measured hepatocyte-related gene expression in mice undergoing partial hepatectomy with or without pretreatment for 1 week with 2-acetyl aminofluorene (AAF). Hepatectomy induced several genes related to early hepatic differentiation in bone marrow. Expression of these genes was enhanced by the administration of AAF, whereas genes specific for mature hepatocytes were not detected. We characterised the bone marrow cell population expressing hepatocyte differentiation genes. alpha-fetoprotein mRNA was induced in Lin- and either CD34+, c-kit+, Sca-1+, CD49f+ or CD45+ cells. The genes upregulated in the liver after AAF treatment and hepatectomy were identified using oligonucleotide microarrays. These included genes associated with the acute phase response. Dexamethasone inhibited the expression of early hepatic differentiation genes in the bone marrow of AAF/PHx mice. Early hepatic differentiation genes were induced in bone marrow in response to hepatectomy, especially when regeneration of the remnant liver was suppressed. Circulating signals generated in the AAF/PHx liver might activate this differentiation.