The transcription factor Grainyhead like 3 (GRHL3) affects endothelial cell apoptosis and migration in a NO-dependent manner
The transcription factor Grainyhead like 3 (GRHL3) affects endothelial cell apoptosis and migration in a NO-dependent manner
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DOI：
10.1016/j.bbrc.2011.08.018
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发表时间：
2011-09-09
影响因子：
3.1
通讯作者：
Haendeler, Judith
中科院分区：
文献类型：
--
作者：
Lukosz, Margarete;Mlynek, Arne;Haendeler, Judith
迁移能力和抗凋亡能力对于适当的内皮功能至关重要。在乳腺癌细胞系中筛选抗凋亡基因时，我们鉴定了Grainyhead like 3（GRHL3）。因此，我们的研究目的是调查是否GRHL3在内皮细胞中表达，并确定其在迁移，凋亡和衰老中的作用。GRHL3在人内皮细胞中表达。GRHL3是内皮细胞迁移所必需的。其机制与血管内皮生长因子无关。GRHL3诱导Akt和内皮型一氧化氮合酶磷酸化，其表达通过生理浓度的一氧化氮增加。一氧化氮依赖性迁移完全依赖于GRHL 3的表达。此外，GRHL3以eNOS依赖的方式抑制内皮细胞的凋亡。因此，GRHL3的缺失可能导致体内内皮功能障碍。人们可以考虑新的治疗策略，目的是保存血管系统中的GRHL 3表达。(C)2011 Elsevier Inc. All rights reserved.
Migratory capacity and resistance to apoptosis are crucial for proper endothelial function. In a screen for anti-apoptotic genes in a breast cancer cell line, we identified Grainyhead like 3 (GRHL3). Therefore, the aim of our study was to investigate whether GRHL3 is expressed in endothelial cells and moreover, to determine its role in migration, apoptosis and senescence. GRHL3 is expressed in human endothelial cells. GRHL3 is required for endothelial cell migration. The underlying mechanism is independent of vascular endothelial growth factor. GRHL3 induces Akt and endothelial nitric oxide synthase phosphorylation and its expression is increased by physiological concentrations of nitric oxide. Nitric oxide dependent migration is completely dependent on GRHL3 expression. Moreover, GRHL3 inhibits apoptosis of endothelial cells in an eNOS-dependent manner. Thus, loss of GRHL3 may result in endothelial dysfunction in vivo. One may consider new therapeutic strategies with the aim to conserve GRHL3 expression in the vasculature. (C) 2011 Elsevier Inc. All rights reserved.