Tomiya T, Ogata I, Fujiwara K
First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Am J Pathol. 1998 Sep;153(3):955-61. doi: 10.1016/s0002-9440(10)65637-4.
Transforming growth factor alpha (TGFalpha) and hepatocyte growth factor (HGF) are mitogens for hepatocytes in vitro and in vivo, produced by hepatocytes or nonparenchymal cells such as stellate cells in the liver. It is still uncertain whether TGFalpha and HGF are essential for liver regeneration. To assess the role of these growth factors in liver regeneration, their circulating and hepatic levels were studied in various rat models of liver regeneration. Hepatic and plasma HGF levels were increased with increased number of mitotic hepatocytes in rats after partial hepatectomy or carbon tetrachloride intoxication. However, hepatic HGF levels were decreased despite an increased number of mitotic hepatocytes and increased or unchanged plasma HGF levels in rats given phenobarbital and in rats after dimethylnitrosamine intoxication, which can induce hepatic necrosis after apoptosis of hepatic stellate cells. In contrast, hepatic and serum TGFalpha levels were increased in all of the models. In sham-operated rats with no increased number of mitotic hepatocytes, hepatic and circulating levels of HGF were increased, whereas those levels of TGFalpha were unchanged. The results indicate that TGFalpha levels in liver and blood more closely correlate with hepatocyte mitogenesis than HGF levels.
转化生长因子α（TGFα）和肝细胞生长因子（HGF）在体外和体内均为肝细胞的促有丝分裂原，由肝细胞或非实质细胞（如肝脏中的星状细胞）产生。TGFα和HGF对肝脏再生是否必不可少仍不确定。为评估这些生长因子在肝脏再生中的作用，在各种肝脏再生大鼠模型中研究了它们的循环水平和肝脏水平。在部分肝切除或四氯化碳中毒后的大鼠中，随着有丝分裂肝细胞数量的增加，肝脏和血浆中的HGF水平升高。然而，在给予苯巴比妥的大鼠以及二甲基亚硝胺中毒后的大鼠中，尽管有丝分裂肝细胞数量增加且血浆HGF水平升高或不变，但肝脏HGF水平却降低，二甲基亚硝胺中毒可在肝星状细胞凋亡后诱导肝坏死。相反，在所有模型中肝脏和血清TGFα水平均升高。在有丝分裂肝细胞数量未增加的假手术大鼠中，肝脏和循环中的HGF水平升高，而TGFα水平未变。结果表明，肝脏和血液中的TGFα水平与肝细胞有丝分裂的相关性比HGF水平更密切。
