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

Mol Med Rep. 2021 Apr;23(4):238. doi: 10.3892/mmr.2021.11877. Epub 2021 Feb 4.

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.

Keywords: corneal neovascularization; platelet‑derived growth factor‑BB; endothelial cells; macrophage.

MeSH terms

  • Alkalies / toxicity*
  • Animals
  • Becaplermin / metabolism*
  • Cell Line
  • Corneal Injuries / chemically induced*
  • Corneal Injuries / metabolism
  • Corneal Injuries / pathology
  • Corneal Neovascularization / chemically induced
  • Corneal Neovascularization / metabolism*
  • Corneal Neovascularization / pathology
  • Humans
  • Mice
  • Receptors, Platelet-Derived Growth Factor / metabolism*
  • Signal Transduction / drug effects

Substances

  • Alkalies
  • Becaplermin
  • Receptors, Platelet-Derived Growth Factor

Grants and funding

The present study was supported by the National Natural Science Foundation in China (grant nos. 81970830, 81671641, 81200727 and 31600736), Suzhou Municipal Natural Science Foundation (grant no. SYS201745), Jiangsu Provincial Medical Youth Talent (grant no. QNRC2016718), Jiangsu Provincial Medical Innovation Team (grant no. CXTDA2017039) and the Soochow Scholar Project of Soochow University (grant no. R5122001).