Transmembrane protein 215 promotes angiogenesis by maintaining endothelial cell survival.
Transmembrane protein 215 promotes angiogenesis by maintaining endothelial cell survival.
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跨膜蛋白 215 通过维持内皮细胞存活促进血管生成
DOI：
10.1002/jcp.27641
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发表时间：
2019-06
影响因子：
5.6
通讯作者：
Han H
中科院分区：
文献类型：
--
作者：
Liu Y;Zheng Q;He G;Zhang M;Yan X;Yang Z;Zhang P;Wang L;Liu J;Liang L;Han H
萌芽血管生成是遭受缺氧和其他相关应激的组织的新血管形成的主要形式。内皮细胞（Endothelial cells，ECs）在血管新生过程中经历增殖、分化、程序性死亡和迁移等过程，但其在血管新生中的分子调控机制尚未完全阐明。在这里，我们报告，跨膜蛋白215（TMEM 215）参与血管生成，通过调节EC的生存。小鼠TMEM 215基因具有两个转录起始位点，通过5′-快速扩增互补DNA（cDNA）末端（RACE）确定，编码双通道TMEM。通过定量逆转录-聚合酶链反应在EC和其他组织中检测到TMEM 215转录物。免疫荧光显示TMEM 215在视网膜、肝脏和肿瘤的血管中表达，并且与EC标记物共定位。我们发现，敲低内皮细胞中的TMEM 215在体外诱导内皮细胞的强烈细胞死亡，而不影响细胞增殖和迁移，这表明TMEM 215是内皮细胞存活所必需的。TMEM 215表达下调损害体外EC的管腔形成和发芽能力。此外，玻璃体内注射TMEM 215小干扰RNA导致视网膜血管发育延迟和异常，灌注不良。这些结果将TMEM 215鉴定为通过调节EC的存活而参与血管生成的新分子。
Sprouting angiogenesis is a major form of neovascularization of tissues suffering from hypoxia and other related stress. Endothelial cells (ECs) undergo proliferation, differentiation, programmed death, and migration during angiogenic sprouting, but the underlying molecular mechanisms regulating ECs in angiogenesis have been incompletely elucidated. Here we report that the transmembrane protein 215 (TMEM215) is involved in angiogenesis by regulating EC survival. The murine TMEM215 gene, which possesses two transcriptional starting sites as determined by 5′‐rapid amplification of complementary DNA (cDNA) ends (RACE), encodes a two‐pass TMEM. The TMEM215 transcripts were detected in ECs in addition to other tissues by quantitative reverse transcription‐polymerase chain reaction. Immunofluorescence showed that TMEM215 was expressed in the vasculature in retina, liver, and tumor, and colocalized with EC markers. We show that knockdown of TMEM215 in ECs induced strong cell death of ECs in vitro without affecting cell proliferation and migration, suggesting that TMEM215 was required for EC survival. Downregulation of TMEM215 expression compromised lumen formation and sprouting capacities of ECs in vitro. Moreover, intravitreous injection of TMEM215 small interfering RNA resulted in delayed and abnormal development of retinal vasculature with poor perfusion. These results identified TMEM215 as a novel molecule involved in angiogenesis by regulating the survival of ECs.
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影响因子：
16.6
作者：
Aspalter IM;Gordon E;Dubrac A;Ragab A;Narloch J;Vizán P;Geudens I;Collins RT;Franco CA;Abrahams CL;Thurston G;Fruttiger M;Rosewell I;Eichmann A;Gerhardt H
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Carmeliet, Peter
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通讯作者：
Carmeliet, Peter
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20.1
作者：
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通讯作者：
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