Transforming growth factor-beta 1 (TGF-beta1) induces angiogenesis through vascular endothelial growth factor (VEGF)-mediated apoptosis.
Transforming growth factor-beta 1 (TGF-beta1) induces angiogenesis through vascular endothelial growth factor (VEGF)-mediated apoptosis.
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DOI：
10.1002/jcp.21706
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发表时间：
2009-05
影响因子：
5.6
通讯作者：
Mignatti, Paolo
中科院分区：
文献类型：
--
作者：
Ferrari, Giovanni;Cook, Brandoch D.;Terushkin, Vitaly;Pintucci, Giuseppe;Mignatti, Paolo
VEGF和TGF-β1诱导血管生成，但对内皮细胞具有相反的作用。VEGF保护内皮细胞免于凋亡; TGF-β1诱导凋亡。我们先前已经证明VEGF / VEGF受体-2（VEGFR 2）信号转导介导TGF-β1诱导细胞凋亡。这一发现提出了一个重要的问题：这种机制是否刺激或抑制血管生成？在这里，我们报告VEGF介导的凋亡是TGF-β1诱导血管生成所必需的。在体外，TGF-β1对内皮细胞的凋亡作用是快速的，随后是细胞对TGF-β1诱导的凋亡不敏感的长时间。抑制VEGF /VEGFR 2信号传导可消除TGF-β1形成索状结构，其作用与细胞凋亡抑制剂z-VAD相当。类似地，VEGF的遗传缺陷消除了TGF-β1上调内皮细胞分化和胚状体中血管结构的形成。体内TGF-β1诱导内皮细胞凋亡的速度与体外一样快。抑制VEGF可阻断TGF-β1诱导细胞凋亡和血管生成，其作用与z-VAD相似。因此，TGF-β1诱导血管生成需要VEGF/VEGFR 2介导的快速和短暂的凋亡作用。VEGF和VEGFR 2的这种新的、意想不到的作用表明VEGF介导的细胞凋亡是控制血管生成的潜在靶点。
VEGF and TGF-β1 induce angiogenesis but have opposing effects on endothelial cells. VEGF protects endothelial cells from apoptosis; TGF-β1 induces apoptosis. We have previously shown that VEGF / VEGF receptor-2 (VEGFR2) signaling mediates TGF-β1 induction of apoptosis. This finding raised an important question: Does this mechanism stimulate or inhibit angiogenesis? Here we report that VEGF-mediated apoptosis is required for TGF-β1 induction of angiogenesis. In vitro the apoptotic effect of TGF-β1 on endothelial cells is rapid and followed by a long period in which the cells are refractory to apoptosis induction by TGF-β1. Inhibition of VEGF / VEGFR2 signaling abrogates formation of cord-like structures by TGF-β1 with an effect comparable to that of z-VAD, an apoptosis inhibitor. Similarly, genetic deficiency of VEGF abolishes TGF-β1 upregulation of endothelial cell differentiation and formation of vascular structures in embryoid bodies. In vivo TGF-β1 induces endothelial cell apoptosis as rapidly as in vitro. Inhibition of VEGF blocks TGF-β1 induction of both apoptosis and angiogenesis, an effect similar to that of z-VAD. Thus, TGF-β1 induction of angiogenesis requires a rapid and transient apoptotic effect mediated by VEGF/VEGFR2. This novel, unexpected role of VEGF and VEGFR2 indicates VEGF-mediated apoptosis as a potential target to control angiogenesis.
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影响因子：
8.7
作者：
Balconi, G;Spagnuolo, R;Dejana, E
通讯作者：
Dejana, E
影响因子：
20.3
作者：
Bautch, VL;Redick, SD;Rapoport, R
通讯作者：
Rapoport, R
DOI：
10.1097/01.asn.0000061779.70530.06
发表时间：
2003-05-01
影响因子：
13.6
作者：
Fierlbeck, W;Liu, AL;Ballermann, BJ
通讯作者：
Ballermann, BJ
影响因子：
11.4
作者：
Goumans, MJ;Valdimarsdottir, G;ten Dijke, P
通讯作者：
ten Dijke, P
影响因子：
3.3
作者：
Anders, RA;Arline, SL;Leof, EB
通讯作者：
Leof, EB