Matrix metalloproteinase 14 participates in corneal lymphangiogenesis through the VEGF-C/VEGFR-3 
signaling pathway

Du,Hai‑Tao; Liu,Ping

doi:10.3892/etm.2016.3601

Matrix metalloproteinase 14 participates in corneal lymphangiogenesis through the VEGF-C/VEGFR-3 signaling pathway

Authors:
- Hai‑Tao Du
- Ping Liu
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Affiliations: Department of Ophthalmology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
Published online on: August 22, 2016 https://doi.org/10.3892/etm.2016.3601
Pages: 2120-2128
Copyright: © Du 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 roles of matrix metalloproteinase 14 (MMP-14) in corneal inflammatory lymphangiogenesis. The expression of MMP-14 in vivo was detected by immunohistochemistry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays, under various corneal conditions. pCMV‑MMP‑14 or empty pCMV vectors were injected into mouse corneal stroma, 3 days after suture placement in a standard suture‑induced inflammatory corneal neovascularization assay. The outgrowth of blood and lymphatic vessels and macrophage recruitment were analyzed using immunofluorescence. The expression levels of vascular endothelial growth factor (VEGF) subtypes were tested by RT-qPCR. MMP‑14 expression was upregulated significantly following various corneal injuries. The results demonstrated, for the first time, that MMP‑14 strongly promotes corneal lymphangiogenesis and macrophage infiltration during inflammation. Furthermore, expression levels of VEGF‑C and VEGF receptor‑3, but not other VEGF components, were significantly upregulated by the intrastromal delivery of MMP‑14 during corneal lymphangiogenesis. In conclusion, this study indicates that MMP‑14 is critically involved in the processes of lymphangiogenesis. Inhibition of MMP‑14 may provide a viable treatment for transplant rejection and other lymphatic disorders.

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