Delayed liver regeneration with negative regulation of hepatocyte growth factor and positive regulation of transforming growth factor-beta1 mRNA after portal branch ligation in biliary obstructed rats.
BACKGROUND
The influence of obstructive jaundice on liver regeneration is still controversial. The aim of this study was to investigate liver regeneration after portal branch ligation (PBL) in the jaundiced rat, focusing on hepatocyte growth factor (HGF) and transforming growth factor-beta1 (TGF-beta 1).


METHODS
Male Wistar rats underwent PBL or a sham operation 7 days after a common bile duct ligation. Liver wet weight, proliferating cell nuclear antigen labeling, HGF and TGF-beta 1 mRNA expression, and immunohistochemical staining with alpha-smooth muscle actin antibody were studied.


RESULTS
The rate of liver regeneration in jaundiced liver was decreased as compared to a non-jaundiced liver. DNA synthesis in the jaundiced non-ligated lobe was significantly lower than in the non-jaundiced liver as was the peak level of HGF mRNA expression after PBL. In contrast, the level of TGF-beta 1 mRNA expression was higher in the jaundiced liver, and alpha-smooth muscle actin staining showed that hepatic stellate cells were gradually activated into myofibroblast-like cells.


CONCLUSIONS
Obstructive jaundice decreased the expression of HGF mRNA and increased the expression of TGF-beta 1 mRNA, resulting in delayed liver regeneration after PBL. We suggest that hepatic stellate cells activated in obstructive jaundice may affect the expression of these growth factors.
Yamano
Toshihisa
T
Department of Surgery II, Okayama University, School of Medicine, Okayama, Japan.
Hirai
Ryuji
R
Hato
Shinji
S
Uemura
Tadahiro
T
Shimizu
Nobuyoshi
N
D000199:Actins / Q000032:analysis; D000818:Animals; D001663:Bilirubin / Q000097:blood; D002779:Cholestasis / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D004247:DNA / Q000096:biosynthesis; D005786:Gene Expression Regulation; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D007150:Immunohistochemistry; D008026:Ligation; D008115:Liver Regeneration; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000235:genetics*
D000199:Actins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor; D004247:DNA; D001663:Bilirubin