Netrin-1: Focus on its role in cardiovascular physiology and atherosclerosis.
Netrin-1: Focus on its role in cardiovascular physiology and atherosclerosis.
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DOI：
10.1177/2048004020959574
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发表时间：
2020-01
影响因子：
1.6
通讯作者：
Ferro A
中科院分区：
文献类型：
--
作者：
Claro V;Ferro A
netrin形成层粘连蛋白相关蛋白家族，其首先被描述为在胎儿发育期间细胞迁移和轴突引导的调节剂。Netrin-1是该家族中研究最广泛的成员，自从其被发现以来，非神经功能一直与其相关。与其受体DCC/neogenin和UNC 5一起，netrin-1已被证明参与血管生成，器官发生，癌症和炎症的调节。内皮细胞和某些类型的癌细胞中也产生了一种NF-κ B依赖性netrin-1的截短亚型，它在细胞核中积累并影响细胞核的功能。在动脉粥样硬化中，netrin-1通过其受体UNC 5 b对斑块进展的作用相互矛盾。尽管内皮衍生的netrin-1抑制白细胞的趋化性并减少单核细胞向动脉粥样硬化斑块的迁移，但斑块内巨噬细胞表达的netrin-1发挥促动脉粥样硬化作用，促进细胞存活，募集平滑肌细胞并抑制泡沫细胞流出至淋巴系统。相反，有证据表明netrin-1促进巨噬细胞分化为另一种活化表型，并诱导IL-4和IL-13的表达，同时下调IL-6和考克斯-2的表达。需要进一步的工作来阐明netrin-1的两种亚型在动脉粥样硬化背景下不同细胞类型中的确切作用，以及其作为这种疾病中推定的新型治疗靶点的潜力。
The netrins form a family of laminin-related proteins which were first described as modulators of cell migration and axonal guidance during fetal development. Netrin-1 is the most extensively studied member of this family and, since its discovery, non-neural roles have been associated with it. Together with its receptors, DCC/neogenin and UNC5, netrin-1 has been shown to be involved in the regulation of angiogenesis, organogenesis, cancer and inflammation. An NF-κB-dependent truncated isoform of netrin-1 has also been shown to be produced in endothelial and some types of cancer cells, which both accumulates in and affects the function of the nucleus. In atherosclerosis, conflicting roles for netrin-1 have been reported on plaque progression via its receptor UNC5b. Whereas endothelial-derived netrin-1 inhibits chemotaxis of leukocytes and reduces the migration of monocytes to the atherosclerotic plaque, netrin-1 expressed by macrophages within the plaque plays a pro-atherogenic role, promoting cell survival, recruiting smooth muscle cells and inhibiting foam cell egress to the lymphatic system. In contrast, there is evidence that netrin-1 promotes macrophage differentiation to an alternative activated phenotype and induces expression of IL-4 and IL-13, while downregulate expression of IL-6 and COX-2. Further work is needed to elucidate the precise roles of the two isoforms of netrin-1 in different cell types in the context of atherosclerosis, and its potential as a putative novel therapeutic target in this disease.
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影响因子：
11.2
作者：
Akino T;Han X;Nakayama H;McNeish B;Zurakowski D;Mammoto A;Klagsbrun M;Smith E
通讯作者：
Smith E
影响因子：
5.3
作者：
Boyer NP;Gupton SL
通讯作者：
Gupton SL
影响因子：
4
作者：
Chen, Qiang;Sun, Xiaqin;Wang, Jia-huai
通讯作者：
Wang, Jia-huai
影响因子：
11.4
作者：
Llambi, F;Causeret, F;Mehlen, P
通讯作者：
Mehlen, P
DOI：
10.1006/bbrc.2000.2583
发表时间：
2000-05-10
影响因子：
3.1
作者：
Kappler, J;Franken, S;Koch, KW
通讯作者：
Koch, KW