Water influx through aquaporin-1 (AQP-1) has been linked to the ability of different cell types to migrate, and therefore plays an important part in processes like metastasis and angiogenesis. Since the erythroid growth factor erythropoietin (Epo) is now recognized as an angiogenesis promoter, we investigated the participation of AQP-1 as a downstream effector of this cytokine in the migration of endothelial cells. Inhibition of AQP-1 with either mercury ions (Hg2+) or a specific siRNA led to an impaired migration of EA.hy926 endothelial cells exposed to Epo (wound-healing assays). Epo also induced the expression of AQP-1 at mRNA and protein levels, an effect which was dependent on the influx of extracellular calcium through L-type calcium channels as well as TRPC3 channels. The relationship between Epo and AQP-1 was further confirmed at shorter exposure times, as the cytokine was unable to trigger calcium influxes in cells where AQP-1 had previously been knocked down. Moreover, Epo promoted changes in the subcellular localization of AQP-1 as well as rearrangements in the actin cytoskeleton, which are consistent with a migratory phenotype. Worthy of note, carbamylated erythropoietin (cEpo), the non-erythropoietic and non-promigratory derivative of Epo, was incapable of AQP-1 modulation. The therapeutical implications of aquaporin targeting in angiogenesis-related diseases highlight the importance of the present results in the context of the relationship between AQP-1 and Epo.

中文翻译：

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Aquaporin-1在促红细胞生成素诱导的内皮细胞迁移中起关键作用。

通过aquaporin-1（AQP-1）流入的水与不同细胞类型的迁移能力有关，因此在转移和血管生成等过程中起着重要作用。由于红细胞生长因子促红细胞生成素（Epo）现在被认为是血管生成促进剂，因此我们研究了AQP-1作为该细胞因子在内皮细胞迁移中的下游效应子的参与。汞离子（Hg2 +）或特异性siRNA对AQP-1的抑制作用导致暴露于Epo的EA.hy926内皮细胞迁移受损（伤口愈合分析）。Epo还诱导了AQP-1在mRNA和蛋白水平上的表达，这种作用取决于通过L型钙通道和TRPC3通道的细胞外钙的流入。Epo和AQP-1之间的关系在更短的暴露时间内得到了进一步证实，因为细胞因子无法触发先前敲低AQP-1的细胞中的钙内流。此外，Epo促进了AQP-1亚细胞定位的变化以及肌动蛋白细胞骨架的重排，这与迁移表型一致。值得注意的是，氨基甲酸酯化的促红细胞生成素（cEpo）是Epo的非促红细胞和非扩散性衍生物，不能进行AQP-1调节。水通道蛋白靶向在血管生成相关疾病中的治疗意义突出了本研究结果在AQP-1与Epo之间的关系中的重要性。Epo促进了AQP-1亚细胞定位的变化以及肌动蛋白细胞骨架的重排，这与迁移表型一致。值得注意的是，氨基甲酸酯化的促红细胞生成素（cEpo）是Epo的非促红细胞和非扩散性衍生物，不能进行AQP-1调节。水通道蛋白靶向在血管生成相关疾病中的治疗意义突出了本研究结果在AQP-1与Epo之间的关系中的重要性。Epo促进了AQP-1亚细胞定位的变化以及肌动蛋白细胞骨架的重排，这与迁移表型一致。值得注意的是，氨基甲酸酯化的促红细胞生成素（cEpo）是Epo的非促红细胞和非扩散性衍生物，不能进行AQP-1调节。水通道蛋白靶向在血管生成相关疾病中的治疗意义突出了本研究结果在AQP-1与Epo之间的关系中的重要性。