Epithelium-derived miR-204 inhibits corneal neovascularization
Epithelium-derived miR-204 inhibits corneal neovascularization
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上皮源性 miR-204 抑制角膜新生血管形成
DOI：
10.1016/j.exer.2017.12.001
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发表时间：
2018-02-01
影响因子：
3.4
通讯作者：
Shi, Weiyun
中科院分区：
文献类型：
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作者：
Zhang, Xiaoping;Di, Guohu;Shi, Weiyun
microRNA-204（miR-204）在角膜中高度表达，本文探讨了miR-204在角膜新生血管形成（CNV）中的作用及其机制。通过结膜下注射miR-204阿戈米尔或阴性对照在BALB/c小鼠中基质内放置缝线来诱导小鼠CNV。以人原代角膜缘上皮细胞（LEC）和永生化微血管内皮细胞（HMEC）为研究对象，探讨miR-204在生物力学应力（BS）作用下的表达变化及其抗血管生成作用。采用实时荧光定量PCR、原位杂交、免疫组化和Western blot检测miR-204、血管内皮生长因子（VEGF）及其受体的表达和定位。结果显示，miR-204主要在角膜上皮中表达，在血管化角膜中表达下调。结膜下注射miR-204 agomir可抑制CNV并降低VEGF和VEGF受体2的表达。类似地，miR-204过表达减弱了LEC中由生物力学应力引起的VEGF表达增加，并抑制了HMEC的增殖、迁移和管形成。这些新发现表明，上皮来源的miR-204通过调节VEGF和VEGF受体2抑制缝线诱导的CNV。
MicroRNA-204 (miR-204) is highly expressed in cornea, here we explored the role and mechanism of miR-204 in corneal neovascularization (CNV). Mouse CNV was induced by intrastromal placement of suture in BALB/c mice with the subconjunctival injection of miR-204 agomir or negative control. Human primary limbal epithelial cells (LECs) and immortalized microvascular endothelial cells (HMECs) were used to evaluate the expression changes and anti-angiogenic effects of miR-204 under biomechanical stress (BS). The expression and localization of miR-204, vascular endothelial growth factor (VEGF) and their receptors were detected by quantitative real-time PCR, in situ hybridization, immunohistochemistry and Western blot. The results showed that miR-204 expression was mainly localized in epithelium and down-expressed in vascularized cornea. Subconjunctival injection of miR-204 agomir inhibited CNV and reduced the expression of VEGF and VEGF receptor 2. Similarly, miR-204 over expression attenuated the increased expression of VEGF by biomechanical stress in LECs, and suppressed the proliferation, migration, and tube formation of HMECs. These novel findings indicate that epithelium-derived miR-204 inhibits suture-induced CNV through regulating VEGF and VEGF receptor 2.