Vascular endothelial growth factor-A is a survival factor for nucleus pulposus cells in the intervertebral disc

Vascular endothelial growth factor-A is a survival factor for nucleus pulposus cells in the intervertebral disc
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DOI:
10.1016/j.bbrc.2008.05.044
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发表时间:
2008-07-25
影响因子:
3.1
通讯作者:
Miyamoto, Takeshi
Miyamoto, Takeshi
中科院分区:
生物学4区
文献类型:
--
作者:
Fujita, Nobuyuki;Imai, Jun-ichi;Miyamoto, Takeshi

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椎间盘(IVD)由两种无血管组织类型组成,即髓核(NP)和纤维环(AF)。IVD是人体中最大的无血管组织,然而,这些组织在没有血液供应的情况下如何维持却知之甚少。在这里,我们表明,血管内皮生长因子-A(VEGF-A)是高表达的NP和VEGF-A在NP的生存发挥作用。微阵列分析检测到NP中VEGF-A的高表达,并且NP对低氧探针pimonidazole和低氧应答基因呈阳性。在体外低氧条件下,NP中VEGF-A的表达被促进。NP细胞还表达膜结合的VEGF受体-1(VEGFR-1),并且在用将VEGF-A捕获在NP中的VEGFR-1-Fc处理后,NP的培养细胞模型中的凋亡细胞的数量增加。这些结果表明NP是一种缺氧组织,VEGF-A以自分泌/旁分泌方式在NP存活中发挥作用。(C)2008年爱思唯尔公司All rights reserved.
The intervertebral disc (IVD) is composed of two avascular tissue types, the nucleus pulposus (NP) and the annulus fibrosus (AF). IVDs is the largest avascular tissue in the human body, however, how these tissues are maintained without a blood supply is poorly understood. Here we show that vascular endothelial growth factor-A (VEGF-A) is highly expressed in NP and that VEGF-A plays a role in NP survival. High VEGF-A expression in NP was detected by microarray analysis, and NP was positive for the hypoxic probe pimonidazole and hypoxia-responsive genes. VEGF-A expression in NP was promoted by hypoxic conditions in vitro. NP cells also expressed the membrane-bound VEGF receptor-1 (VEGFR-1), and the number of apoptotic cells in cultured cell model of NP increased following treatment with VEGFR-1-Fc, which traps VEGF-A in NP. These results indicate that NP is a hypoxic tissue, and that VEGF-A functions in NP survival in an autocrine/paracrine manner. (C) 2008 Elsevier Inc. All rights reserved.