The Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China.
Exp Eye Res. 2012 Dec;105:15-20. doi: 10.1016/j.exer.2012.10.004. Epub 2012 Oct 16.
Neovascularization is the critical pathological process and the leading cause of blindness in a variety of clinical conditions. This angiogenesis process is still uncertain. Human hepatocyte growth factor 1 (HGFK1) is derived from the mature form of hepatocyte growth factor, which contains four kringle domains in its α-chain. This study aimed to investigate the antiangiogenic activity of HGFK1 using in vitro and in vivo assays. HGFK1 was added into the DMEM to test the proliferation and migration of human umbilical vascular endothelial cells (HUVEC), and it was intravitreously injected in laser photocoagulation-induced choroidal neovascularization (NV) model, oxygen-induced retinopathy model and rho/VEGF transgenic mice to test its antiangiogenic effect. The results showed that HGFK1 effectively inhibited VEGF-stimulated HUVEC proliferation and migration, and also had anti-NV activity in choroidal NV and retinal NV. It is suggested that HGFK1 has antiangiogenic activity in vitro and in vivo. It may lead to new potential drug discoveries and the development in addition to anti-VEGF therapy in the future clinical anti-angiogenesis treatment.
血管新生是多种临床情况下的关键病理过程和致盲的主要原因。这一血管生成过程仍不明确。人肝细胞生长因子 1（HGFK1）来源于成熟的肝细胞生长因子，其α链包含四个kringle 结构域。本研究旨在通过体外和体内实验来研究 HGFK1 的抗血管生成活性。将 HGFK1 添加到 DMEM 中，检测人脐静脉内皮细胞（HUVEC）的增殖和迁移，然后将其玻璃体内注射到激光光凝诱导的脉络膜新生血管（NV）模型、氧诱导的视网膜病变模型和 rho/VEGF 转基因小鼠中，以检测其抗血管生成作用。结果表明，HGFK1 能有效抑制 VEGF 刺激的 HUVEC 增殖和迁移，在脉络膜 NV 和视网膜 NV 中也具有抗 NV 活性。这表明 HGFK1 在体外和体内均具有抗血管生成活性。它可能会导致新的潜在药物发现，并在未来的临床抗血管生成治疗中除抗 VEGF 治疗之外得到进一步发展。
