Inhibition of PDGF-BB Reduces Alkali-Induced Corneal Neovascularization in Mice
Molecular Medicine Reports(2021)
摘要
The aim of the present study was to investigate the role of platelet-derived growth factor (PDGF)-BB/PDGF receptor (R)-beta signaling in an experimental murine corneal neovascularization (CrNV) model. Experimental CrNV was induced by alkali injury. The intra-corneal expression of PDGF-BB was examined using immunohistochemistry. The effect of PDGF-BB on CrNV was evaluated using immunofluorescence staining. The expression levels of PDGFR-beta in human retinal endothelial cells (HRECs) under normal conditions or following cobalt chloride treatment, which induced hypoxic conditions, was assessed using reverse transcription-quantitative PCR. The effect of exogenous treatment of PDGF-BB on the proliferation, migration and tube formation of HRECs under normoxic or hypoxic conditions was evaluated in vitro using Cell Counting Kit-8, wound healing and 3D Matrigel capillary tube formation assays, respectively. The results indicated that the intra-corneal expression levels of the proteins of PDGF-BB and PDGFR-beta were detectable on days 2 and 7 following alkali injury. The treatment with neutralizing anti-PDGF-BB antibody resulted in significant inhibition of CrNV. The intra-corneal expression levels of vascular endothelial growth factor A, matrix metallopeptidase (MMP)-2 and MMP-9 proteins were downregulated, while the expression levels of thrombospondin (TSP)-1, TSP-2, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-1 and ADAMTS-2 were upregulated significantly in mice treated with anti-PDGF-BB antibody. The expression levels of PDGFR-beta were upregulated in HRECs under hypoxic conditions compared with those noted under normoxic conditions. Recombinant human PDGF-BB promoted the proliferation, migration and tube formation of HRECs under hypoxic conditions. The data indicated that PDGF-BB/PDGFR-beta signaling was involved in CrNV and that it promoted endothelial cell proliferation, migration and tube formation. The pro-angiogenic effects of this pathway may be mediated via the induction of pro-angiogenic cytokine secretion and the suppression of anti-angiogenic cytokine secretion.
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关键词
corneal neovascularization,platelet-derived growth factor-BB,endothelial cells,macrophage
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