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【medical-news】AIP1是小鼠体内VEGFR2中介的信号和炎
http://www.jci.org/articles/view/36168
ASK1-interacting protein-1 (AIP1), a recently identified member of the Ras GTPase-activating protein family, is highly expressed in vascular ECs and regulates EC apoptosis in vitro. However, its function in vivo has not been established. To study this, we generated AIP1-deficient mice (KO mice). Although these mice showed no obvious defects in vascular development, they exhibited dramatically enhanced angiogenesis in 2 models of inflammatory angiogenesis. In one of these models, the enhanced angiogenesis observed in the KO mice was associated with increased VEGF-VEGFR2 signaling. Consistent with this, VEGF-induced ear, cornea, and retina neovascularization were greatly augmented in KO mice and the enhanced retinal angiogenesis was markedly diminished by overexpression of AIP1. In vitro, VEGF-induced EC migration was inhibited by AIP1 overexpression, whereas it was augmented by both AIP1 knockout and knockdown, with the enhanced EC migration caused by AIP1 knockdown being associated with increased VEGFR2 signaling. We present mechanistic data that suggest AIP1 is recruited to the VEGFR2-PI3K complex, binding to both VEGFR2 and PI3K p85, at a late phase of the VEGF response, and that this leads to inhibition of VEGFR2 signaling. Taken together, our data demonstrate that AIP1 functions as an endogenous inhibitor in VEGFR2-mediated adaptive angiogenesis in mice. 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 嗯~~~看来血管方面的研究，确实关注的人少啊。哈哈，我自己认领吧。 AIP1 functions as an endogenous inhibitor of VEGFR2-mediated signaling and inflammatory angiogenesis in mice
AIP1是小鼠体内VEGFR2中介的信号和炎症性血管生成的内源性抑制因子
ASK1-interacting protein-1 (AIP1), a recently identified member of the Ras GTPase-activating protein family, is highly expressed in vascular ECs and regulates EC apoptosis in vitro. However, its function in vivo has not been established. To study this, we generated AIP1-deficient mice (KO mice). Although these mice showed no obvious defects in vascular development, they exhibited dramatically enhanced angiogenesis in 2 models of inflammatory angiogenesis. In one of these models, the enhanced angiogenesis observed in the KO mice was associated with increased VEGF-VEGFR2 signaling. Consistent with this, VEGF-induced ear, cornea, and retina neovascularization were greatly augmented in KO mice and the enhanced retinal angiogenesis was markedly diminished by overexpression of AIP1. In vitro, VEGF-induced EC migration was inhibited by AIP1 overexpression, whereas it was augmented by both AIP1 knockout and knockdown, with the enhanced EC migration caused by AIP1 knockdown being associated with increased VEGFR2 signaling. We present mechanistic data that suggest AIP1 is recruited to the VEGFR2-PI3K complex, binding to both VEGFR2 and PI3K p85, at a late phase of the VEGF response, and that this leads to inhibition of VEGFR2 signaling. Taken together, our data demonstrate that AIP1 functions as an endogenous inhibitor in VEGFR2-mediated adaptive angiogenesis in mice.
最近新发现的Ras GTPase激活蛋白家族的成员----ASK1相互作用蛋白1(AIP1)，在体外的血管内皮细胞中高度表达，并调节细胞的凋亡。然而，其体内的功能未知。为了研究这一点，我们孕育了AIP1缺陷小鼠（KO鼠）。尽管这些小鼠没有显示出血管发育方面的缺陷，但是，在两个炎症性血管生成模型中，它们表现出极大的血管生成能力。其中一个模型，在KO小鼠内观察到血管生成升高并伴随着VEGF-VEGFR2信号的增加。与此一致，在KO小鼠，VEGF诱导的耳、角膜和视网膜新生血管化也有极大的增强，在视网膜过表达AIP1后，血管生成明显降低。体外，VEGF诱导的内皮细胞迁移也被AIP1过表达明显抑制，而无论是AIP1敲除和降低表达时迁移都会增强，并且在AIP1降低表达导致内皮细胞迁移增强时伴随有VEGFR2信号的增强。我们提供了机械的 mechanistic data：有关机理方面的数据 [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-08-22 06:36
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