Therapeutic effects of topical netrin-4 inhibits corneal neovascularization in alkali-burn rats.
Therapeutic effects of topical netrin-4 inhibits corneal neovascularization in alkali-burn rats.
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外用 Netrin-4 抑制碱烧伤大鼠角膜新生血管的治疗作用
DOI：
10.1371/journal.pone.0122951
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Han Y;Shao Y;Liu T;Qu YL;Li W;Liu Z
Netrin是参与轴突导向和血管生成的分泌分子。然而，netrins在脉管系统中的作用仍不清楚。已经发现Netrin-4和netrin-1是促血管生成因子或抗血管生成因子。以前，我们发现netrin-1作为一种抗血管生成因子在大鼠中通过抑制碱烧伤诱导的角膜新生血管。在这里，我们进一步研究netrin-4，同一netrin家族的另一个成员，在体外和体内对新血管形成的影响。我们发现netrin-4在血管生成中的功能与netrin-1相似。体外血管生成实验表明，netrin-4以剂量依赖方式影响人脐静脉内皮细胞（HUVEC）的管腔形成、活力和增殖、凋亡、迁移和侵袭。在第0天（损伤后立即）和/或损伤后第10天，将Netrin-4在体内局部应用于碱烧伤的大鼠角膜。Netrin-4随后抑制并逆转角膜新生血管形成。Netrin-4抑制角膜上皮和基质细胞凋亡，抑制血管内皮生长因子（VEGF），但促进色素上皮衍生因子（PEDF）表达，降低NK-KB p65表达，并抑制中性粒细胞和巨噬细胞浸润。这些结果表明，netrin-4揭示了其在治疗影响眼表以及其他组织的血管生成性疾病中的潜在作用。
Netrins are secreted molecules involved in axon guidance and angiogenesis. However, the role of netrins in the vasculature remains unclear. Netrin-4 and netrin-1 have been found to be either pro- or antiangiogenic factors. Previously, we found that netrin-1 acts as an anti-angiogenic factor in rats by inhibiting alkali burn-induced corneal neovascularization. Here, we further investigate the effects of netrin-4, another member of the same netrin family, on neovascularization in vitro and in vivo. We found that netrin-4 functions similarly as netrin-1 in angiogenesis. In vitro angiogenesis assay shows that netrin-4 affected human umbilical vein endothelial cell (HUVEC) tube formation, viability and proliferation, apoptosis, migration, and invasion in a dose-dependent manner. Netrin-4 was topically applied in vivo to alkali-burned rat corneas on day 0 (immediately after injury) and/or day 10 post-injury. Netrin-4 subsequently suppressed and reversed corneal neovascularization. Netrin-4 inhibited corneal epithelial and stromal cell apoptosis, inhibited vascular endothelial growth factor (VEGF), but promoted pigment epithelium-derived factor (PEDF) expression, decreased NK-KB p65 expression, and inhibits neutrophil and macrophage infiltration. These results indicate that netrin-4 shed new light on its potential roles in treatmenting for angiogenic diseases that affect the ocular surface, as well as other tissues.
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影响因子：
2.1
作者：
Laria, C;Alio, JL;RuizMoreno, JM
通讯作者：
RuizMoreno, JM
影响因子：
11.8
作者：
Castets, Marie;Coissieux, Marie-May;Mehlen, Patrick
通讯作者：
Mehlen, Patrick
影响因子：
5.7
作者：
Bijman, Marcel N. A.;van Nieuw Amerongen, Geerten P.;Boven, Epie
通讯作者：
Boven, Epie
影响因子：
6.3
作者：
Hoang, Stanley;Liauw, Jason;Steinberg, Gary K.
通讯作者：
Steinberg, Gary K.
影响因子：
20.3
作者：
Larrieu-Lahargue, Frederic;Welm, Alana L.;Li, Dean Y.
通讯作者：
Li, Dean Y.