Angiogenesis Mediated by Toll-Like Receptor 4 in Ischemic Neural Tissue
Angiogenesis Mediated by Toll-Like Receptor 4 in Ischemic Neural Tissue
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缺血神经组织中 Toll 样受体 4 介导的血管生成
DOI：
10.1161/atvbaha.112.300679
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发表时间：
2013-02-01
影响因子：
8.7
通讯作者：
Liu, Xialin
中科院分区：
文献类型：
--
作者：
He, Chang;Sun, Yuying;Liu, Xialin
通过Toll样受体（TLR）激活免疫系统与动脉粥样硬化、微血管并发症和血管生成有关。然而，TLR参与缺血神经组织中炎症相关的血管生成尚未研究。本研究的目的是确定TLR 4信号转导在氧诱导的视网膜新生血管中的作用，视网膜是一种神经tissue.Methods和Results-In氧诱导的视网膜病变模型，我们发现，视网膜新生血管显着衰减TLR 4（-/-）小鼠。进一步的研究表明，TLR 4的缺乏导致促炎因子的下调，这与缺血视网膜中胶质细胞的活化减弱有关，这也与TLR 4的内源性配体高迁移率族蛋白-1的表达减少有关。将高迁移率族蛋白-1应用于缺血性视网膜促进了野生型小鼠促炎因子的产生，但对TLR 4-/-小鼠没有促进作用。高迁移率族蛋白-1治疗在体外也显着促进生产的促炎因子在视网膜神经胶质细胞从野生型小鼠，但少得多从TLR 4（-/-）mice. Conclusion，我们的研究结果表明，高迁移率族蛋白-1在缺血性神经组织中的释放启动TLR 4依赖的反应，有助于新血管形成。这些发现代表了以前未被认识到的TLR 4对缺血神经组织中与胶质细胞活化相关的血管生成的作用。（Arterioscler Thromb Vasc Biol.2013;33：330-338.）
Objective-Activation of the immune system via toll-like receptors (TLRs) is implicated in atherosclerosis, microvascular complications, and angiogenesis. However, the involvement of TLRs in inflammation-associated angiogenesis in ischemic neural tissue has not been investigated. The goal of this study is to determine the role of TLR4 signaling in oxygen-induced neovascularization in retina, a neural tissue.Methods and Results-In oxygen-induced retinopathy model, we found that retinal neovascularization was significantly attenuated in TLR4(-/-) mice. The further study revealed that the absence of TLR4 led to downregulation of proinflammatory factors in association with the attenuated activation of glia in the ischemic retina, which was also associated with reduced expression of high-mobility group box-1, an endogenous ligand for TLR4. The application of high-mobility group box-1 to the ischemic retina promoted the production of proinflammatory factors in wild-type but not TLR4-/- mice. High-mobility group box-1 treatment in vitro also significantly promoted the production of proinflammatory factors in retinal glial cells from wild-type mice, but much less from TLR4(-/-) mice.Conclusion-Our results suggest that the release of high-mobility group box-1 in ischemic neural tissue initiates TLR4-dependent responses that contribute to neovascularization. These findings represented a previously unrecognized effect of TLR4 on angiogenesis in association with the activation of glia in ischemic neural tissue. (Arterioscler Thromb Vasc Biol. 2013;33:330-338.)