Expression and localization of basic fibroblast growth factor (bFGF) in the repair process of rat liver injury.
OBJECTIVE
To clarify the expression and localization of basic fibroblast growth factor in the repair process of liver injury, acute liver injury was induced by administration of carbon tetrachloride, D-glactosamine hydrochloride, or dimethylnitrosamine to rats.


METHODS
We measured basic fibroblast growth factor protein in the liver tissue by radioimmunoassay, evaluated the expression of basic fibroblast growth factor mRNA by the reverse transcriptase polymerase chain reaction, and identified basic fibroblast growth factor-positive cells by immunostaining.


RESULTS
In the carbon tetrachloride injured liver, the basic fibroblast growth factor protein contents began to increase 2 days after administration when liver injury was most marked, and reached a peak after 4 days, decreasing thereafter. In the carbon tetrachloride-injured liver, basic fibroblast growth factor mRNA expression was observed from 12 h after administration, prior to an increase in the protein content. In the D-galactosamine hydrochloride-injured liver, basic fibroblast growth factor protein also increased. On the other hand, in the dimethylnitrosamine-injured liver, the basic fibroblast growth factor protein content decreased 2 days after administration when liver injury was marked, but increased after 7 days. In the regenerating liver after partial hepatectomy, the basic fibroblast growth factor protein content did not increase. Among cell fractions, the Ito cell fraction obtained from the carbon tetrachloride-injured liver after 4 days showed expression of basic fibroblast growth factor mRNA. In cells cultured for 24 h, this fraction was immunopositive for basic fibroblast growth factor. Ito cells in the liver tissue markedly increased in the carbon tetrachloride-injured liver and increased after 7 days in the dimethylnitrosamine-injured liver.


CONCLUSIONS
This study confirmed basic fibroblast growth factor production in the liver tissue in the repair process of liver injury. Our results suggest that basic fibroblast growth factor is primarily produced in Ito cells, acts on sinusoidal wall cells including Ito cells by the autocrine and paracrine mechanisms, and promotes extracellular matrix production and vascularization, involving the repair process of liver injury.
Hioki
O
O
Third Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Ishikawa, Japan.
Minemura
M
M
Shimizu
Y
Y
Kasii
Y
Y
Nishimori
H
H
Takahara
T
T
Higuchi
K
K
Yoshitake
Y
Y
Nishikawa
K
K
Watanabe
A
A
D000818:Animals; D001483:Base Sequence; D002458:Cell Fractionation; D056486:Chemical and Drug Induced Liver Injury; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000096:biosynthesis*; D008107:Liver Diseases / Q000378:metabolism*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D012194:RNA-Directed DNA Polymerase; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar
D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D012194:RNA-Directed DNA Polymerase