Anti-transforming growth factor-beta1 antibody transiently enhances DNA synthesis during liver regeneration after partial hepatectomy in rats.
The regulation of liver regeneration after partial hepatectomy (PHx) is complex and involves many different cytokines. We investigated the role of one of these, transforming growth factor-beta1 (TGF-beta1), an inhibitor of liver regeneration, in a Wistar male rat model, in which anti-TGF-beta1 antibody was injected immediately or 24 h after 70% PHx. Livers from treated animals contained an increased number of cells in S phase, according to 5-bromo-2'-deoxyuridine (BrdU) labeling 36 h after PHx. Antibody administration 24 h after PHx resulted in the highest peak of proliferation; moreover, peak MIB-5 labeling was also observed at that time. However, neither residual liver-weight-to-body-weight ratios nor regeneration rates differed significantly between any of the animals. Therefore, we also measured levels of serum TGF-beta1 and hepatocyte growth factor (HGF; an activator). With antibody administration at 0 or 24 h, TGF-beta1 levels were diminished at 24 or 36 h as compared with levels in control rats, but then rebounded, reaching a delayed peak at 48 or 72 h after PHx, respectively. Interestingly, there were also similar trends in HGF levels. These results indicate that TGF-beta1 may inhibit the G1 checkpoint, and serum TGF-beta1 concentration may influence HGF to regulate liver regeneration and to maintain homeostasis of proliferation after PHx.
Enami
Y
Y
Second Department of Surgery, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
Kato
H
H
Murakami
M
M
Fujioka
T
T
Aoki
T
T
Niiya
T
T
Murai
N
N
Ohtsuka
K
K
Kusano
M
M
D000704:Analysis of Variance; D000818:Animals; D001323:Autoantibodies / Q000494:pharmacology*; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006498:Hepatectomy / Q000379:methods; D017228:Hepatocyte Growth Factor / Q000097:blood*; D022781:Hepatocytes / Q000502:physiology; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D011336:Probability; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D016212:Transforming Growth Factor beta / Q000097:blood / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D001323:Autoantibodies; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017228:Hepatocyte Growth Factor; D004247:DNA