Vascular Endothelial Growth Factor-A (VEGF-A) Mediates Activin A-Induced Human Trophoblast Endothelial-Like Tube Formation

Endocrinology
Yan LiPeter C K Leung

Abstract

Remodeling of maternal spiral arteries during pregnancy requires a subpopulation of extravillous cytotrophoblasts (EVTs) to differentiate into endovascular EVTs. Activin A, which is abundantly expressed at the maternal-fetal interface, has been shown to promote trophoblast invasion, but its role in endovascular differentiation remains unknown. Vascular endothelial growth factor-A (VEGF-A) is well recognized as a key regulator in trophoblast endovascular differentiation. Whether and how activin A might regulate VEGF-A production in human trophoblasts and its relationship to endovascular differentiation have yet to be determined. In the present study, we found that activin A increased VEGF-A production in primary and immortalized (HTR8/SVneo) human EVT cells. In addition, activin A enhanced HTR8/SVneo endothelial-like tube formation, and these effects were attenuated by pretreatment with small interfering RNA targeting VEGF-A or the VEGF receptor 1/2 inhibitor SU4312. Pretreatment with the activin/TGF-β type 1 receptor (ALK4/5/7) inhibitor SB431542 abolished the stimulatory effects of activin A on phosphorylated mothers against decapentaplegic (SMAD)-2/3 phosphorylation, VEGF-A production, and endothelial-like tube formation. Mor...Continue Reading

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Citations

Jun 29, 2017·Journal of Cellular Biochemistry·Jimena S BeltrameMaría L Ribeiro
Dec 13, 2018·Physiological Reviews·Enrrico BloiseFernando M Reis
Oct 27, 2018·Journal of Cellular Physiology·Jimena S BeltrameMaría L Ribeiro
Aug 16, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Asghar AliQuinton A Winger
Jan 5, 2020·Biology of Reproduction·Lindsey N BlockJenna Kropp Schmidt
Jan 8, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hong-Jin ZhaoPeter C K Leung
Jun 14, 2018·Experimental and Therapeutic Medicine·Xuena CuiYuanhua Ye
Jun 18, 2020·Reproductive Sciences·Eugene D Albrecht, Gerald J Pepe
Nov 12, 2020·International Journal of Molecular Sciences·Rebekah R StarksGeetu Tuteja

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