Macrophage-derived netrin-1 is critical for neuroangiogenesis in endometriosis
Macrophage-derived netrin-1 is critical for neuroangiogenesis in endometriosis
复制标题
巨噬细胞衍生的 netrin-1 对于子宫内膜异位症的神经血管生成至关重要
DOI：
10.1016/j.ijbiomac.2020.01.130
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发表时间：
2020-04-01
影响因子：
8.2
通讯作者：
Zhang, Xinmei
中科院分区：
文献类型：
--
作者：
Guo, Xinyue;Ding, Shaojie;Zhang, Xinmei
Netrin-1是神经元导航的细胞外引导因子，通过与其主要受体的相互作用介导，并且已知在多种慢性炎性疾病的发展中至关重要。然而，netrin-1在子宫内膜异位症中的表达模式和机制目前尚不清楚。在这里，我们报告netrin-1的表达在子宫内膜异位症的腹腔巨噬细胞中达到峰值。Netrin-1通过与血管内皮细胞中的CD 146相互作用诱导卵巢腺瘤中的血管生成。netrin-1通过另一种受体再生素，通过上调MAP 4、TAU和CGRP促进子宫内膜异位症中神经突的生长和致敏。靶向敲除背根神经节（DRG）神经细胞中的再生蛋白通过抑制ERK 1/2的磷酸化来损害其对netrin-1的反应。使用中和抗体抑制netrin-1可减少大鼠动脉粥样硬化病变中的血管和神经浸润。总之，我们的研究结果表明netrin-1是促进子宫内膜异位症神经血管生成的重要因素。(C)2020 Elsevier B. V.保留所有权利。
Netrin-1 is an extracellular guidance cue of neuronal navigation, mediated through interaction with its main receptors, and is known to be crucial in the development of multiple chronic inflammatory diseases. However, the expression pattern and mechanism of netrin-1 in endometriosis are currently undefined. Here we report that netrin-1 expression peaked in peritoneal macrophages found in endometriosis. Netrin-1 induced angiogenesis in ovarian endometriomas through interaction with CD146 in vascular endothelial cells. Through another receptor, neogenin, netrin-1 promoted neurite growth and sensitization in endometriosis through the up-regulation of MAP4, TAU, and CGRP. Targeted knockdown of neogenin in dorsal root ganglion (DRG) nerve cells compromised its response to netrin-1 through inhibiting phosphorylation of ERK1/2. The inhibition of netrin-1 using a neutralizing antibody reduced vascular and nerve infiltration in rat endometriotic lesions. In summary, our results suggest that netrin-1 is an important factor that promotes neuroangiogenesis in endometriosis. (C) 2020 Elsevier B.V. All rights reserved.