Hepatocyte growth factor and transforming growth factor beta1 contribute to regeneration of small-for-size liver graft immediately after transplantation.
Although the ability of the liver to regenerate to a predetermined size after resection made adult-to-adult living donor liver transplantation (LDLT) possible, there is little information regarding the growth regulatory mechanism for a small-for-size graft. Forty-one cases of LDLT were divided into two groups by graft volume to standard liver volume ratio (GV/SLV); small graft group (Group S, GV/SLV<40%, n=16) and non-small graft group (Group NS, GV/SLV>40%, n=25). The regeneration rate (GV at 1 week/harvested GV) and serum levels of hepatocyte growth factor (HGF), transforming growth factor-alpha (TGF-alpha) and transforming growth factor-beta1 (TGF-beta1) were compared between two groups. The regeneration rates in Group S were significantly higher than that of Group NS (217+/-12% and 178+/-10%, respectively, P<0.01). The serum HGF levels of Group S were significantly higher than those of Group NS on POD 1. The TGF-beta1 levels of Group S were significantly higher than those of Group NS on POD 3 and 5. The TGF-alpha levels were not different at any time points studied. These results indicate that a small-for-size graft retains the capacity to regenerate faster by modulation of expression pattern of HGF and TGF-beta1 immediately after LDLT. After the acceleration of the regenerative response by HGF, subsequent elevation of TGF-beta1 synergistically controls graft size, regulating uncontrolled proliferation of hepatocytes.
Ninomiya
Mizuki
M
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan. nnmym@surg2.med.kyushu-u.ac.jp
Harada
Noboru
N
Shiotani
Satoko
S
Hiroshige
Shoji
S
Minagawa
Ryosuke
R
Soejima
Yuji
Y
Suehiro
Taketoshi
T
Nishizaki
Takashi
T
Shimada
Mitsuo
M
Sugimachi
Keizo
K
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D017228:Hepatocyte Growth Factor / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000503:physiopathology; D008115:Liver Regeneration; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D016211:Transforming Growth Factor alpha / Q000097:blood; D016212:Transforming Growth Factor beta / Q000097:blood / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
C508960:TGFB1 protein, human; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017228:Hepatocyte Growth Factor