VEGF Induces Expression of Genes That Either Promote or Limit Relaxation of the Retinal Endothelial Barrier.
VEGF Induces Expression of Genes That Either Promote or Limit Relaxation of the Retinal Endothelial Barrier.
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DOI：
10.3390/ijms24076402
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发表时间：
2023-03-29
影响因子：
5.6
通讯作者：
Kazlauskas, Andrius
中科院分区：
文献类型：
--
作者：
McCann, Maximilian;Li, Yueru;Baccouche, Basma;Kazlauskas, Andrius
本研究的目的是鉴定介导VEGF诱导的通透性的基因。我们对在正常（5 mM）和高葡萄糖（30 mM）条件下培养的原代人视网膜内皮细胞（HREC）进行了RNA-Seq分析，所述HREC用载体、VEGF或VEGF然后抗VEGF处理。我们筛选了我们的RNA-Seq数据集，以鉴定具有以下四个特征的基因：（1）受VEGF调节，（2）抗VEGF逆转VEGF调节，（3）在正常和高葡萄糖条件下受VEGF调节，以及（4）已知对血管稳态的贡献。在所得的18个基因中，选择Notch信号传导途径和ANGPT 2（Ang 2）的成员用于进一步研究。渗透性测定显示，虽然Notch途径被认为是放松屏障，但它有助于维持开放的屏障。相反，Ang 2限制了响应VEGF的屏障松弛的程度。这些发现表明VEGF与不同的基因组结合以诱导和维持屏障松弛。此外，VEGF诱导限制屏障松弛程度的基因的表达。总之，这些观察开始阐明VEGF介导的通透性转录调节的优雅。
The purpose of this study was to identify genes that mediate VEGF-induced permeability. We performed RNA-Seq analysis on primary human retinal endothelial cells (HRECs) cultured in normal (5 mM) and high glucose (30 mM) conditions that were treated with vehicle, VEGF, or VEGF then anti-VEGF. We filtered our RNA-Seq dataset to identify genes with the following four characteristics: (1) regulated by VEGF, (2) VEGF regulation reversed by anti-VEGF, (3) regulated by VEGF in both normal and high glucose conditions, and (4) known contribution to vascular homeostasis. Of the resultant 18 genes, members of the Notch signaling pathway and ANGPT2 (Ang2) were selected for further study. Permeability assays revealed that while the Notch pathway was dispensable for relaxing the barrier, it contributed to maintaining an open barrier. In contrast, Ang2 limited the extent of barrier relaxation in response to VEGF. These findings indicate that VEGF engages distinct sets of genes to induce and sustain barrier relaxation. Furthermore, VEGF induces expression of genes that limit the extent of barrier relaxation. Together, these observations begin to elucidate the elegance of VEGF-mediated transcriptional regulation of permeability.
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DOI：
10.1124/jpet.105.086553
发表时间：
2005-08-01
影响因子：
3.5
作者：
Roviezzo, F;Tsigkos, S;Papapetropoulos, A
通讯作者：
Papapetropoulos, A
影响因子：
15.9
作者：
Kim, Minah;Allen, Breanna;McDonald, Donald M.
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影响因子：
14.9
作者：
McCarthy DJ;Chen Y;Smyth GK
通讯作者：
Smyth GK
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影响因子：
20.1
作者：
Aman, Jurjan;Margadant, Coert
通讯作者：
Margadant, Coert
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y