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

doi:10.3892/mmr.2021.11877

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

Authors:
- Lei Chen
- Hongya Wu
- Chi Ren
- Gaoqin Liu
- Wenpeng Zhang
- Weiming Liu
- Peirong Lu
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Affiliations: Department of Ophthalmology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Jiangsu Key Laboratory of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
Published online on: January 28, 2021 https://doi.org/10.3892/mmr.2021.11877
Article Number: 238
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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