Enami Y, Kato H, Murakami M, Fujioka T, Aoki T, Niiya T, Murai N, Ohtsuka K, Kusano M
Second Department of Surgery, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
J Hepatobiliary Pancreat Surg. 2001;8(3):250-8. doi: 10.1007/s005340170025.
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.
部分肝切除术后肝脏再生的调控是复杂的，涉及许多不同的细胞因子。我们在Wistar雄性大鼠模型中研究了其中一种细胞因子——转化生长因子β1（TGF-β1，一种肝脏再生抑制剂）的作用，在该模型中，在70%部分肝切除术后立即或24小时注射抗TGF-β1抗体。根据部分肝切除术后36小时的5-溴-2'-脱氧尿苷（BrdU）标记，处理组动物肝脏中处于S期的细胞数量增加。部分肝切除术后24小时给予抗体导致增殖高峰最高；此外，此时也观察到MIB-5标记的峰值。然而，任何一组动物之间的残余肝重与体重之比或再生率均无显著差异。因此，我们还测量了血清TGF-β1和肝细胞生长因子（HGF，一种激活剂）的水平。在0或24小时给予抗体时，与对照大鼠相比，TGF-β1水平在24或36小时降低，但随后反弹，分别在部分肝切除术后48或72小时达到延迟峰值。有趣的是，HGF水平也有类似趋势。这些结果表明，TGF-β1可能抑制G1期检查点，血清TGF-β1浓度可能影响HGF以调节肝脏再生并维持部分肝切除术后增殖的稳态。
