NF-κB-inducing kinase is a key regulator of inflammation-induced and tumour-associated angiogenesis.
NF-κB-inducing kinase is a key regulator of inflammation-induced and tumour-associated angiogenesis.
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DOI：
10.1002/path.4403
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发表时间：
2014-11
影响因子：
7.3
通讯作者：
Tas, Sander W.
中科院分区：
文献类型：
--
作者：
Noort, Ae R.;van Zoest, Katinka P. M.;Weijers, Ester M.;Koolwijk, Pieter;Maracle, Chrissta X.;Novack, Deborah V.;Siemerink, Martin J.;Schlingemann, Reinier O.;Tak, Paul P.;Tas, Sander W.
血管生成在发育过程和病理条件（如慢性炎症和癌症进展）中是必不可少的。通过靶向血管内皮生长因子（VEGF）抑制血管生成可阻断疾病进展，但大多数患者最终会产生代偿性信号通路导致的耐药性。在内皮细胞（ECs）中，促血管生成趋化因子CXCL12的表达受非典型核因子(NF)-κB信号传导调节。在这里，我们报告了NF-κB诱导激酶（NIK）和随后的非规范NF-κB信号传导调节炎症诱导和肿瘤相关的血管生成。NIK在肿瘤组织和炎症类风湿性关节炎滑膜组织的内皮细胞（ECs）中高度表达。此外，人微血管内皮细胞中的非典型NF-κB信号显著增强了血管管的形成，而这一过程被靶向NIK的siRNA完全阻断。有趣的是，Nik - / -小鼠在发育过程中表现出正常的血管生成，tnf - α或vegf诱导的血管生成反应没有改变，而非典型NF-κ b刺激诱导的血管生成明显减少。此外，实验性关节炎和小鼠肿瘤模型的血管生成在这些小鼠中严重受损。这些研究为非典型NF-κB信号在病理性血管生成中的作用提供了证据，并确定NIK是慢性炎症疾病和肿瘤新生血管生成的潜在治疗靶点。©2014作者。由John Wiley & Sons Ltd代表大不列颠和爱尔兰病理学会出版的病理学杂志。
Angiogenesis is essential during development and in pathological conditions such as chronic inflammation and cancer progression. Inhibition of angiogenesis by targeting vascular endothelial growth factor (VEGF) blocks disease progression, but most patients eventually develop resistance which may result from compensatory signalling pathways. In endothelial cells (ECs), expression of the pro-angiogenic chemokine CXCL12 is regulated by non-canonical nuclear factor (NF)-κB signalling. Here, we report that NF-κB-inducing kinase (NIK) and subsequent non-canonical NF-κB signalling regulate both inflammation-induced and tumour-associated angiogenesis. NIK is highly expressed in endothelial cells (ECs) in tumour tissues and inflamed rheumatoid arthritis synovial tissue. Furthermore, non-canonical NF-κB signalling in human microvascular ECs significantly enhanced vascular tube formation, which was completely blocked by siRNA targeting NIK. Interestingly, Nik−/− mice exhibited normal angiogenesis during development and unaltered TNFα- or VEGF-induced angiogenic responses, whereas angiogenesis induced by non-canonical NF-κB stimuli was significantly reduced. In addition, angiogenesis in experimental arthritis and a murine tumour model was severely impaired in these mice. These studies provide evidence for a role of non-canonical NF-κB signalling in pathological angiogenesis, and identify NIK as a potential therapeutic target in chronic inflammatory diseases and tumour neoangiogenesis. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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影响因子：
8.8
作者：
通讯作者：
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影响因子：
4.4
作者：
Drayton, DL;Bonizzi, G;Ruddle, NH
通讯作者：
Ruddle, NH
DOI：
10.1084/jem.20011565
发表时间：
2002-05-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
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通讯作者：
Weyand CM
影响因子：
64.8
作者：
KIM, KJ;LI, B;FERRARA, N
通讯作者：
FERRARA, N
影响因子：
56.9
作者：
Gao, Dingcheng;Nolan, Daniel J.;Mittal, Vivek
通讯作者：
Mittal, Vivek