- 标题
- 摘要
- 关键词
- 实验方案
- 产品
-
Essential contribution of macrophage Tie2 signal mediated autophagy in laser-induced choroidal neovascularization
摘要： Autophagy plays critical roles in various ocular diseases, including age-related macular degeneration (AMD). Tie2-expressing macrophages (TEMs) play crucial roles in angiogenesis. To investigate the role of TEMs and autophagy in the development of AMD, we employed macrophage-specific Tie2 knockout mice and used a laser-induced choroidal neovascularization (CNV). The results showed that TEMs can promote CNV formation by up-regulating the level of autophagy. These results were further verified by in vitro cell experiments that peritoneal macrophages from Tie2 knockout mice can inhibit the expression of autophagy-related factors and inhibit the expression of angiogenic factor of VEGF by activating AMPK signaling pathway. Our results suggest that TEMs and macrophage Tie2 signal mediated-autophagy play critical role in experimental CNV, and they may be novel preventive targets for AMD treatment.
关键词： Tie2-expressing macrophage (TEMs),Age-related macular degeneration,Choroidal neovascularization,Autophagy
更新于2025-09-23 15:19:57
-
Imaging of Tie2 with a Fluorescently Labeled Small Molecule Affinity Ligand
摘要： The receptor tyrosine kinase inhibitor, Tie2, has significant roles in endothelial signaling and angiogenesis, and is relevant in the pathophysiology of several diseases. However, there are relatively few small molecule probes available to study Tie2, making evaluation of its activity in vivo difficult. Recently, it was discovered that the small molecule, rebastinib (DCC-2036), is a potent Tie2 inhibitor. We hypothesized that fluorescent derivatives of rebastinib could be used as imaging agents for Tie2. Based on crystallography structures, we synthesized three fluorescent derivatives, which we then evaluated in both in vitro and in vivo assays. We found that the Rebastinib-BODIPY TMR (Reb-TMR) derivative has superior imaging characteristics in vitro, and successfully labeled endothelial cells in vivo. We propose that this probe could be further used in in vivo applications for studying the role of Tie2 in disease.
关键词： small molecule probes,rebastinib,Tie2,imaging agents,fluorescent derivatives,receptor tyrosine kinase,angiogenesis
更新于2025-09-12 10:27:22