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Inhibition of PDGF-BB reduces alkali-induced corneal neovascularization in mice

The aim of the present study was to investigate the role of platelet-derived growth factor (PDGF)-BB/PDGF receptor (R)-β 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 u...

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Autores principales: Chen, Lei, Wu, Hongya, Ren, Chi, Liu, Gaoqin, Zhang, Wenpeng, Liu, Weiming, Lu, Peirong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893695/
https://www.ncbi.nlm.nih.gov/pubmed/33537811
http://dx.doi.org/10.3892/mmr.2021.11877
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author Chen, Lei
Wu, Hongya
Ren, Chi
Liu, Gaoqin
Zhang, Wenpeng
Liu, Weiming
Lu, Peirong
author_facet Chen, Lei
Wu, Hongya
Ren, Chi
Liu, Gaoqin
Zhang, Wenpeng
Liu, Weiming
Lu, Peirong
author_sort Chen, Lei
collection PubMed
description The aim of the present study was to investigate the role of platelet-derived growth factor (PDGF)-BB/PDGF receptor (R)-β 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-β 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-β 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-β 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-β 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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spelling pubmed-78936952021-03-08 Inhibition of PDGF-BB reduces alkali-induced corneal neovascularization in mice Chen, Lei Wu, Hongya Ren, Chi Liu, Gaoqin Zhang, Wenpeng Liu, Weiming Lu, Peirong Mol Med Rep Articles The aim of the present study was to investigate the role of platelet-derived growth factor (PDGF)-BB/PDGF receptor (R)-β 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-β 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-β 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-β 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-β 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. D.A. Spandidos 2021-04 2021-01-28 /pmc/articles/PMC7893695/ /pubmed/33537811 http://dx.doi.org/10.3892/mmr.2021.11877 Text en Copyright: © Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Chen, Lei
Wu, Hongya
Ren, Chi
Liu, Gaoqin
Zhang, Wenpeng
Liu, Weiming
Lu, Peirong
Inhibition of PDGF-BB reduces alkali-induced corneal neovascularization in mice
title Inhibition of PDGF-BB reduces alkali-induced corneal neovascularization in mice
title_full Inhibition of PDGF-BB reduces alkali-induced corneal neovascularization in mice
title_fullStr Inhibition of PDGF-BB reduces alkali-induced corneal neovascularization in mice
title_full_unstemmed Inhibition of PDGF-BB reduces alkali-induced corneal neovascularization in mice
title_short Inhibition of PDGF-BB reduces alkali-induced corneal neovascularization in mice
title_sort inhibition of pdgf-bb reduces alkali-induced corneal neovascularization in mice
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893695/
https://www.ncbi.nlm.nih.gov/pubmed/33537811
http://dx.doi.org/10.3892/mmr.2021.11877
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