期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1867, 期 1, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bbamcr.2019.118569
关键词
Angiogenesis; Aquaporin-1; Calcium; Endothelial cells; Erythropoietin
资金
- University of Buenos Aires [UBACYT 20020170100539BA]
- National Scientific and Technical Research Council (Consejo Nacional de Investigaciones Cientificas y Tecnicas) [CONICET 11220150100804CO]
- National Agency for the Promotion of Science and Technology, Argentina (Agencia Nacional de Promocion Cientifica y Tecnologica) [ANPCYT-PICT 2016-1607]
- CONICET (Argentina)
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.
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