title: Anti-transforming growth factor-beta1 antibody transiently enhances DNA synthesis during liver regeneration after partial hepatectomy in rats.
abstract: 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.
authors.affiliation: Second Department of Surgery, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Enami
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Murakami
authors.forename: T
authors.initials: T
authors.lastname: Fujioka
authors.forename: T
authors.initials: T
authors.lastname: Aoki
authors.forename: T
authors.initials: T
authors.lastname: Niiya
authors.forename: N
authors.initials: N
authors.lastname: Murai
authors.forename: K
authors.initials: K
authors.lastname: Ohtsuka
authors.forename: M
authors.initials: M
authors.lastname: Kusano
mesh_terms: 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
chemical_list: D001323:Autoantibodies; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017228:Hepatocyte Growth Factor; D004247:DNA