Hepatic gene induction in murine bone marrow after hepatectomy.
OBJECTIVE
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Yamazaki
Shintaro
S
Department of Digestive Surgery, Nihon University School of Medicine, Itabashi-ku, Tokyo, 173-8610, Japan.
Miki
Kenji
K
Takayama
Tadatoshi
T
Hasegawa
Kiyoshi
K
Sata
Masataka
M
Midorikawa
Yutaka
Y
Aburatani
Hiroyuki
H
Makuuchi
Masatoshi
M
D015073:2-Acetylaminofluorene / Q000494:pharmacology; D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006498:Hepatectomy; D051536:Hepatocyte Nuclear Factors / Q000235:genetics*; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation; D000509:alpha-Fetoproteins / Q000235:genetics*
D051536:Hepatocyte Nuclear Factors; D012333:RNA, Messenger; D000509:alpha-Fetoproteins; D015073:2-Acetylaminofluorene