The role of VEGF in the development of diabetic retinopathy in dog

当喂食半乳糖时，狗会出现类似糖尿病的视网膜毛细血管变化，包括选择性周细胞丢失、微动脉瘤和视网膜出血。此外，这些早期的毛细血管变化可进展到增生晚期，并明显形成新的血管。在这个项目中，研究了血管内皮生长因子（VEGF）在这种特殊狗模型新血管形成中的潜在作用。在不添加任何生长因子的情况下，狗内皮细胞的细胞存活率明显降低。在培养基中加入VEGF可以保护这些细胞免受生长因子饥饿引起的细胞死亡。同时，VEGF促进犬内皮细胞的管状形成。VEGF的加入也增加了两种VEGF受体Flt-1和KDR/Flk-1的表达，并启动转录因子Elk1的磷酸化。酪氨酸激酶抑制剂Genestein可消除VEGF诱导的Elk1磷酸化和细胞生长。这些数据证实了VEGF能刺激犬视网膜毛细血管内皮细胞的细胞生长和成管。VEFG还增加受体KDR和Flt-1的表达，激活p44/42 MAP激酶途径

When fed with galactose, dogs develop diabetes-like retinal capillary changes that include selective pericyte loss, microaneurysms and retinal hemorrhages. In addition, these early capillary changes can progress to the advanced proliferative stage with apparent new vessel formation. In this project, the potential role of vascular endothelial growth factor (VEGF) in the formation of new vessels of this particular dog model has been investigated. When cultured without any growth factors, cell survival of dog endothelial cells is significantly reduced. Addition of VEGF into the culture media protects these cells from cell death induced by growth factor starvation. At the same time, VEGF enhances tube-like formation of dog endothelial cells. Addition of VEGF also increases the expression of two VEGF receptors Flt-1 and KDR/Flk-1 and initiates the phosphorylation of the transcription factor Elk1. The tyrosine kinase inhibitor Genestein eliminates VEGF induced phosphorylation of Elk1 and cell growth. These data confirm that cell growth and tube formation of dog retinal capillary endothelial cells are stimulated by VEGF. VEFG also increases the expression of the receptors KDR and Flt-1 and activates the p44/42 MAP kinase pathway