Naka D, Ishii T, Shimomura T, Hishida T, Hara H
Biosciences Laboratory, Mitsubishi Kasei Corporation Research Center, Yokohama, Japan.
Exp Cell Res. 1993 Dec;209(2):317-24. doi: 10.1006/excr.1993.1316.
Hepatocyte growth factor (HGF) is a mitogen for hepatocytes, having high affinity for heparin. In this study, we examined the function of cell surface heparin-like molecules in HGF/receptor interaction and HGF-induced mitogenic activity using hepatocytes. Binding studies using 125I-HGF showed that more than 85% of bound HGF was released from the cell surface by washing with heparin. This procedure also released HGF from the c-Met protein, which is a component of the high-affinity receptor. In addition, heparitinase digestion of hepatocytes reduced the HGF bound to c-Met protein. Furthermore, excess heparin added during the binding of 125I-HGF to hepatocytes, significantly diminished HGF bound to c-Met protein. Moreover, when DNA synthesis of hepatocytes was repressed and retarded by excess HGF, exogenous heparin restored it. These results suggest that HGF is bound to c-Met protein and that its mitogenic activity is regulated by heparin-like molecules on hepatocytes.
肝细胞生长因子（HGF）是一种对肝细胞有促有丝分裂作用的因子，对肝素具有高亲和力。在本研究中，我们利用肝细胞研究了细胞表面类肝素分子在HGF/受体相互作用及HGF诱导的促有丝分裂活性中的功能。使用125I-HGF进行的结合研究表明，超过85%结合的HGF可通过用肝素洗涤从细胞表面释放。该过程还能从作为高亲和力受体组成部分的c-Met蛋白上释放HGF。此外，对肝细胞进行类肝素酶消化可减少与c-Met蛋白结合的HGF。再者，在125I-HGF与肝细胞结合过程中添加过量肝素，会显著减少与c-Met蛋白结合的HGF。而且，当过量HGF抑制并阻碍肝细胞的DNA合成时，外源性肝素可使其恢复。这些结果表明，HGF与c-Met蛋白结合，且其促有丝分裂活性受肝细胞上类肝素分子的调节。
