The Role of the Wnt Pathway in VEGF/Anti-VEGF-Dependent Control of the Endothelial Cell Barrier.
The Role of the Wnt Pathway in VEGF/Anti-VEGF-Dependent Control of the Endothelial Cell Barrier.
复制标题
Wnt通路在内皮细胞屏障的VEGF/抗VEGF依赖性控制中的作用。
DOI：
10.1167/iovs.62.12.17
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发表时间：
2021-09-02
影响因子：
4.4
通讯作者：
Kazlauskas A
中科院分区：
文献类型：
--
作者：
Li Y;Baccouche B;Olayinka O;Serikbaeva A;Kazlauskas A
研究Wnt途径对血管内皮生长因子（VEGF）/抗VEGF介导的内皮细胞渗透性控制的贡献。将高糖处理的原代人视网膜内皮细胞（HREC）暴露于VEGF或VEGF然后抗VEGF。通过RNAseq和qRT-PCR测定基因表达的变化。通过电细胞基质阻抗传感（ECIS）监测渗透性。激活Wnt通路的方法包括用LiCl处理和组成性激活的β-连环蛋白的过表达。在稳定表达TCF/LEF驱动报告基因的HREC中监测β-连环蛋白依赖性转录活性。VEGF/抗VEGF改变了编码Wnt途径许多成员的基因的表达。这些基因的一个子集被调节的方式可能有助于控制内皮细胞屏障。也就是说，VEGF诱导的这些基因表达的改变被抗VEGF逆转，并且这种调整发生在与屏障功能变化相对应的时间。虽然激活Wnt通路的药理学和分子方法对基础通透性没有影响，但它们抑制了VEGF诱导的舒张。此外，抗VEGF介导的屏障功能恢复不受Wnt途径激活的影响。VEGF/抗VEGF结合Wnt通路的多个成员，并且激活该通路通过减弱VEGF诱导的松弛来加强内皮屏障。这些数据表明，FDA批准的药物如LiCl可能是抗VEGF治疗包括糖尿病视网膜病变在内的致盲患者的辅助药物。
Investigate the contribution of the Wnt pathway to vascular endothelial growth factor (VEGF)/anti-VEGF-mediated control of endothelial cell permeability. High glucose-treated primary human retinal endothelial cells (HRECs) were exposed to either VEGF, or VEGF and then anti-VEGF. Changes in gene expression were assayed by RNAseq and qRT-PCR. Permeability was monitored by electrical cell-substrate impedance sensing (ECIS). Approaches to activate the Wnt pathway included treatment with LiCl and overexpression of constitutively activated β-catenin. β-catenin-dependent transcriptional activity was monitored in HRECs stably expressing a TCF/LEF-driven reporter. VEGF/anti-VEGF altered expression of genes encoding many members of the Wnt pathway. A subset of these genes was regulated in a way that is likely to contribute to control of the endothelial cell barrier. Namely, the VEGF-induced alteration of expression of such genes was reversed by anti-VEGF, and such adjustments occurred at times corresponding to changes in barrier function. While pharmacological and molecular approaches to activate the Wnt pathway had no effect on basal permeability, they suppressed VEGF-induced relaxation. Furthermore, anti-VEGF-mediated restoration of barrier function was unaffected by activation of the Wnt pathway. VEGF/anti-VEGF engages multiple members of the Wnt pathway, and activating this pathway enforces the endothelial barrier by attenuating VEGF-induced relaxation. These data suggest that FDA-approved agents such as LiCl may be an adjuvant to anti-VEGF therapy for patients afflicted with blinding conditions including diabetic retinopathy.
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影响因子：
6.7
作者：
Goddard LM;Iruela-Arispe ML
通讯作者：
Iruela-Arispe ML
影响因子：
15.1
作者：
L'episcopo F;Serapide MF;Tirolo C;Testa N;Caniglia S;Morale MC;Pluchino S;Marchetti B
通讯作者：
Marchetti B
影响因子：
2.7
作者：
Bernard, Pascal;Fleming, Alice;Vilain, Eric
通讯作者：
Vilain, Eric
影响因子：
11.4
作者：
Im, Eunok;Kazlauskas, Andrius
通讯作者：
Kazlauskas, Andrius
影响因子：
3.7
作者：
Kolben, Thomas;Peroebner, Iris;Neth, Peter
通讯作者：
Neth, Peter