Effects of HGF and KGF gene silencing on vascular endothelial growth factor and its receptors in rat ultraviolet radiation‑induced corneal neovascularization

He,Min; Han,Tao; Wang,Yan; Wu,Yao‑Hong; Qin,Wei‑Shan; Du,Ling‑Zhen; Zhao,Chang‑Qing

doi:10.3892/ijmm.2019.4114

Effects of HGF and KGF gene silencing on vascular endothelial growth factor and its receptors in rat ultraviolet radiation‑induced corneal neovascularization

Authors:
- Min He
- Tao Han
- Yan Wang
- Yao‑Hong Wu
- Wei‑Shan Qin
- Ling‑Zhen Du
- Chang‑Qing Zhao
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Affiliations: Department of Ophthalmology, The Second Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Clinical Medical College, Second Military Medical University, Shanghai 200433, P.R. China, Bayi Children's Hospital Affiliated to PLA Army General Hospital, Beijing 100700, P.R. China, Department of Otolaryngology, The Second Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
Published online on: February 27, 2019 https://doi.org/10.3892/ijmm.2019.4114
Pages: 1888-1899

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Abstract

Hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF), two paracrine growth factors, modulate corneal epithelial cell metabolism, apoptosis and survival. Vascular endothelial growth factor (VEGF) serves as a proangiogenic factor in corneal neovascularization (CNV), which is a major cause of vision impairment and corneal blindness. The aim of the present study was to evaluate the ability of HGF and KGF to influence VEGF and its receptor, kinase insert domain receptor (Flk‑1) in corneal injury and CNV in rats induced by ultraviolet radiation (UVR). An UVR‑induced corneal injury rat model was successfully established to characterize the expression patterns of KGF, HGF, VEGF and Flk‑1 in corneal tissues. Corneal epithelial cells were extracted and treated with small interfering RNAs (siRNAs) targeting KGF, HGF or both (si‑KGF, si‑HGF or si‑HGF/KGF). The effects of HGF and KGF were examined through detection of the expression of KGF, HGF, VEGF and Flk‑1, and the evaluation of cell proliferation, cell cycle and cell apoptosis. The expression levels of KGF, HGF, VEGF and Flk‑1 in corneal tissues were increased in the rat model. In the cell experiments, the transfection of si‑HGF/KGF resulted in reductions in VEGF, Flk‑1, KGF and HGF. In addition, decreased cell proliferation and elevated cell apoptosis were found in the corneal epithelial cells from the rat model following KGF and HGF gene silencing. Taken together, these findings suggest that HGF and KGF gene silencing inhibits UVR‑induced corneal epithelial proliferation and CNV and may function as novel targets for corneal wound healing.

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