Nerve growth factor-endothelial cell interaction leads to angiogenesis in vitro and in vivo
Nerve growth factor-endothelial cell interaction leads to angiogenesis in vitro and in vivo
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DOI：
10.1096/fj.01-1000fje
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发表时间：
2002-06-01
期刊：
影响因子：
4.8
通讯作者：
Bernardini, R
中科院分区：
文献类型：
--
作者：
Cantarella, G;Lempereur, L;Bernardini, R
神经生长因子（Nerve growth factor，NGF）在胚胎发育过程中以及在正常和病理条件下对子宫外生活中的各种组织和器官具有重要作用。RT-PCR和免疫学方法证实人脐静脉内皮细胞（HUVECs）表达神经生长因子受体trkA（NGFR）和p75（NTR）。神经生长因子治疗引起的trkA（NGFR）在HUVEC的快速磷酸化，确定磷酸化ERK 1/2的平行增加。因此，NGF诱导HUVEC增殖的显著增加被trkA（NGFR）抑制剂K252 a消除。此外，HUVEC在标准培养条件下表达显著水平的NGF，其在血清饥饿期间上调。内源性神经生长因子是负责基础水平的trkA（NGFR）和ERK 1/2磷酸化观察未处理的HUVEC培养。最后，当将NGF递送到鸡胚的绒毛尿囊膜上时，其在体内发挥了有效的、直接的血管生成活性。这些数据表明，神经生长因子可能在神经系统的血管形成和一些病理过程中发挥重要作用，包括肿瘤和炎性疾病。揭示神经生长因子依赖性血管生成的机制可以为抗血管生成治疗的新方法提供有价值的工具。
Nerve growth factor (NGF) has important functions during embryonic development and on various tissues and organs under normal and pathological conditions during the extrauterine life. RT-PCR analysis and immunological methods demonstrate that human umbilical vein endothelial cells (HUVECs) express the NGF receptors trkA(NGFR) and p75(NTR). NGF treatment caused a rapid phosphorylation of trkA(NGFR) in HUVECs, determining a parallel increase of phosphorylated ERK1/2. Accordingly, NGF induced a significant increase in HUVEC proliferation that was abolished by the trkA(NGFR) inhibitor K252a. Also, HUVECs express significant levels of NGF under standard culture conditions that were up-regulated during serum starvation. Endogenous NGF was responsible for the basal levels of trkA(NGFR) and ERK1/2 phosphorylation observed in untreated HUVEC cultures. Finally, NGF exerted a potent, direct, angiogenic activity in vivo when delivered onto the chorioallantoic membrane of the chicken embryo. The data indicate that NGF may play an important role in blood vessel formation in the nervous system and in several pathological processes, including tumors and inflammatory diseases. Unraveling mechanisms of NGF-dependent angiogenesis could provide valuable tools for novel therapeutic approaches in antiangiogenic therapy.