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基质金属蛋白酶14通过VEGF-C/VEGFR-3信号通路参与角膜淋巴管生成。

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

作者信息

Du Hai-Tao, Liu Ping

机构信息

Department of Ophthalmology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.

出版信息

Exp Ther Med. 2016 Oct;12(4):2120-2128. doi: 10.3892/etm.2016.3601. Epub 2016 Aug 22.

DOI:10.3892/etm.2016.3601
PMID:27698700
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5038200/
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 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.

摘要

本研究的目的是探讨基质金属蛋白酶14（MMP - 14）在角膜炎症性淋巴管生成中的作用。在各种角膜条件下，通过免疫组织化学、逆转录定量聚合酶链反应（RT - qPCR）和蛋白质印迹分析检测MMP - 14的表达。在标准缝线诱导的炎症性角膜新生血管形成试验中，在放置缝线3天后，将pCMV - MMP - 14或空pCMV载体注射到小鼠角膜基质中。使用免疫荧光分析血管和淋巴管的生长以及巨噬细胞的募集。通过RT - qPCR检测血管内皮生长因子（VEGF）亚型的表达水平。在各种角膜损伤后，MMP - 14表达显著上调。结果首次表明，MMP - 14在炎症过程中强烈促进角膜淋巴管生成和巨噬细胞浸润。此外，在角膜淋巴管生成过程中，通过基质内递送MMP - 14，VEGF - C和VEGF受体 - 3的表达水平显著上调，而其他VEGF成分则未上调。总之，本研究表明MMP - 14在淋巴管生成过程中起关键作用。抑制MMP - 14可能为移植排斥和其他淋巴疾病提供一种可行的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f7e/5038200/4ea0ae82e260/etm-12-04-2120-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f7e/5038200/8e9eaf108a22/etm-12-04-2120-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f7e/5038200/1049c94d225c/etm-12-04-2120-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f7e/5038200/bd7e17b395d7/etm-12-04-2120-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f7e/5038200/8472249c8f10/etm-12-04-2120-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f7e/5038200/4ea0ae82e260/etm-12-04-2120-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f7e/5038200/8e9eaf108a22/etm-12-04-2120-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f7e/5038200/1049c94d225c/etm-12-04-2120-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f7e/5038200/bd7e17b395d7/etm-12-04-2120-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f7e/5038200/8472249c8f10/etm-12-04-2120-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f7e/5038200/4ea0ae82e260/etm-12-04-2120-g04.jpg

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