Hepatocyte growth factor (HGF) is essential for injury repair. Despite high HGF levels in chronic ulcers, up-regulation of HGF receptor in ulcer tissue and decreased biological activity of HGF in ulcer secretions have been observed. With a surface plasmon resonance-based method, we assessed the binding of HGF to antibodies, receptors, and the basement membrane and identified binding interactions that are indispensable for the biological activity of HGF. Recombinant HGF (rHGF) lots were tested for activity, structural integrity, and degradation, and the results were verified in an in vitro model of cell injury. Biologically active rHGF, as well as plasma from healthy volunteers, bound to heparan sulphate proteoglycan (HSPG) and to anti-HGF antibodies. Decreased binding to HSPG was the first event in rHGF degradation. This study established the feasibility of identifying patients with chronic inflammation who need exogenous HGF and of using ligand-binding assessment to evaluate rHGF lots for biological activity.

中文翻译：

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实时评估肝细胞生长因子的生物活性和降解的临床影响。

肝细胞生长因子 (HGF) 对损伤修复至关重要。尽管慢性溃疡中 HGF 水平较高，但已观察到溃疡组织中 HGF 受体的上调和溃疡分泌物中 HGF 的生物活性降低。使用基于表面等离子体共振的方法，我们评估了 HGF 与抗体、受体和基底膜的结合，并确定了对 HGF 生物活性必不可少的结合相互作用。对重组 HGF (rHGF) 批次进行活性、结构完整性和降解测试，结果在体外细胞损伤模型中得到验证。具有生物活性的 rHGF 以及来自健康志愿者的血浆与硫酸乙酰肝素蛋白多糖 (HSPG) 和抗 HGF 抗体结合。与 HSPG 的结合减少是 rHGF 降解的第一个事件。