A novel and effective human hepatocyte growth factor kringle 1 domain inhibits ocular neovascularization

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.

► HGFK1 can inhibit the proliferation and migration of HUVECs induced by VEGF.
► Intravitreous injection of HGFK1 suppresses the growth of choroidal NV induced by laser photocoagulation.
► Intravitreous injection of HGFK1 suppresses ischemia-induced retinal NV.
► Retinal NV which Rho/VEGF transgenic mice develop in the subretinal space can be inhibited by intravitreous injection of HGFK1.