The tetraspanin CD151-ARSA mutant inhibits angiogenesis via the YRSL sequence.

The tetraspanin CD151-ARSA mutant inhibits angiogenesis via the YRSL sequence.
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四跨膜蛋白 CD151-ARSA 突变体通过 YRSL 序列抑制血管生成

DOI:
10.3892/mmr.2012.1250
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发表时间:
2013-03
影响因子:
3.4
通讯作者:
Zhang XA
Zhang XA
中科院分区:
医学4区
文献类型:
--
作者:
Peng D;Zuo H;Liu Z;Qin J;Zhou Y;Li P;Wang D;Zeng H;Zhang XA

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以往的研究表明,四跨膜蛋白CD 151是病理性或生理性血管生成所必需的。然而,CD 151 YRSL分选基序在体外血管发生中的细胞信号传导机制和作用仍然未知。在本研究中,结果显示,CD 151和CD 151-ARSA基因递送能够在蛋白水平上增加人脐静脉内皮细胞(HUVECs)中的CD 151表达。此外,CD 151组和CD 151-ARSA组之间的CD 151蛋白表达无显著差异。CD 151过表达促进HUVEC细胞增殖、迁移和毛细血管网形成。而CD 151-ARSA组细胞增殖、迁移及毛细血管网形成能力均较CD 151组降低。此外,与CD 151组相比,CD 151-ARSA突变体组中PI 3 K、Akt和ERK信号通路的激活减弱。这项研究表明,CD 151的YRSL基序在CD 151诱导的血管生成中起着关键作用。我们的观察提供了一个新的机制,CD 151调节血管生成通过囊泡运输的见解。
Previous studies have shown that the tetraspanin CD151 is essential for pathological or physiological angiogenesis. However, the cellular signaling mechanism and the role of the CD151 YRSL sorting motif in in vitro vasculogenesis remains unknown. In this study, the results showed that both CD151 and CD151-ARSA gene delivery were capable of increasing the expression of CD151 at the protein level in human umbilical vein endothelial cells (HUVECs). Moreover, there was no significant difference in CD151 protein expression between the CD151 group and the CD151-ARSA group. Overexpression of CD151 promoted HUVEC cell proliferation, migration and capillary network formation in vitro. However, in the CD151-ARSA group, the abilities of cell proliferation, migration and capillary network formation were all decreased, compared with the CD151 group. Furthermore, the activation of PI3K, Akt and ERK signaling pathways was attenuated in the CD151-ARSA mutant group compared with the CD151 group. This study suggests that the YRSL motif of CD151 plays a key role in CD151-induced angiogenesis. Our observations provide insights into a new mechanism of CD151 regulating angiogenesis via vesicle trafficking.
DOI: 10.1073/pnas.2536699100
发表时间: 2003-12-23
影响因子: 11.1
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