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Chenyang Zhao, Yusen Liu, Jiayu Meng, Xiaotang Wang, Xianyang Liu, Wanqian Li, Qian Zhou, Junjie Xiang, Na Li, Shengping Hou; LGALS3BP in Microglia Promotes Retinal Angiogenesis Through PI3K/AKT Pathway During Hypoxia. Invest. Ophthalmol. Vis. Sci. 2022;63(8):25. doi: https://doi.org/10.1167/iovs.63.8.25.
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Retinal microglia promote angiogenesis and vasculopathy in oxygen-induced retinopathy (OIR); however, its specific molecular mechanism in the formation of retinal angiogenesis remains unclear. The lectin galactoside-binding soluble 3 binding protein (LGALS3BP), a member of the scavenger receptor cysteine-rich (SRCR) domain protein family, is involved in tumor neovascularization, and we therefore hypothesized that LGALS3BP plays an active role in microglia-induced angiogenesis.
The expression of LGALS3BP in microglia was detected by immunofluorescence, RT-qPCR, and western blotting. Functional assays of human umbilical vein endothelial cells (HUVECs) such as migration, proliferation, and tube formation were measured by Transwell, EdU, and Matrigel assays. Angiogenesis-related factors and PI3K/AKT levels were detected by western blotting. The relationship between LGALS3BP and PI3K or HIF-1α was investigated by immunoprecipitation.
Our results showed that the expression of LGALS3BP was significantly increased in microglia surrounding neovascularization of the OIR mice and was also upregulated in human microglial clone 3 (HMC3) cells after hypoxia. Moreover, HUVECs co-cultured with hypoxic HMC3 cells showed increased migration, proliferation, and tube formation, as well as levels of angiogenesis-related factor. However, the proangiogenic ability and angiogenesis-related factor expression of HMC3 cells was suppressed after silencing LGALS3BP. LGALS3BP induces the upregulation of angiogenesis-related factors through the PI3K/AKT pathway and then promotes angiogenesis in microglia.
Collectively, our findings suggest that LGALS3BP in microglia plays an important role in angiogenesis, suggesting a potential therapeutic target of LGALS3BP for angiogenesis.
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