Upregulation of sFlt-1 by trophoblasts induces the barrier dysfunction of glomerular endothelial cells

Abstract

This study examined the effect of over-expression of sFlt-1 by trophoblasts on the barrier function of glomerular endothelial cells and the role of VEGF in this process in order to explore the pathogenesis of glomerular disease in preeclampsia. SFlt-1 expression in the human trophoblasts (TEV-1 cells) was enhanced by transfecting sFlt-1 plasmid DNA into TEV-1 cells. The monolayer barrier function of glomerular endothelial cells (ciGEnCs) was determined by measuring the fluorescence intensity of bovine serum albumin (BSA) that crossed the monolayer of glomerular endothelial cells. The results showed that the over-expression of sFlt-1 by TEV-1 cells led to the barrier dysfunction of ciGEnCs, and the exogenous VEGF could alleviate the ciGEnCs dysfunction resulting from the over-expression of sFlt-1 to a certain extent. It was concluded that the dysregulation of sFlt-1 and VEGF in preeclamptic pregnancy may contribute to the barrier dysfunction of glomerular endothelial cells, and VEGF may play an important role in maintaining the barrier function of glomerular endothelial cells, but it may not be the sole factor.

Keywords

preeclampsia / trophoblast / glomerular endothelial cell / monolayer barrier function

References

[1] DuckittK., HarringtonD.. Risk factors for pre-eclampsia at antenatal booking: Systematic review of controlled studies. BMJ, 2005, 330(7491): 565

[2] StillmanI.E., KarumanchiS.A.. The glomerular injury of preeclampsia. J Am Soc Nephrol, 2007, 18(8): 2281-2284

[3] HenaoD.E., SaleemM.A., CadavidA.P.. Glomerular disturbances in preeclampsia: disruption between glomerular endothelium and podocyte symbiosis. Hypertens Pregnancy, 2010, 29(1): 10-20

[4] MoranP., BaylisP.H., LindheimerM.D., et al.. Glomerular ultrafiltration in normal and preeclamptic pregnancy. J Am Soc Nephrol, 2003, 14: 648-652

[5] VikseB.E., IrgensL.M., LeivestadT., et al.. Preeclampsia and the risk of end-stage renal disease. N Engl J Med, 2008, 359(8): 800-809

[6] StrevensH., Wide-SwenssonD., HansenA., et al.. Glomerular endotheliosis in normal pregnancy and pre-eclampsia. BJOG, 2003, 110(9): 831-836

[7] KarumanchiS.A., StillmanI.E.. In vivo rat model of preeclampsia. Methods Mol Med, 2006, 122: 393-399

[8] DoiK., NoiriE., FujitaT.. Role of vascular endothelial growth factor in kidney disease. Curr Vasc Pharmacol, 2010, 8(1): 122-128

[9] TangZ., RenH., YangG., et al.. Significance of vascular endothelial growth factor expression in renal tissue of patients with preeclamptic nephropathy. Am J Nephrol, 2005, 25(6): 579-585

[10] WakelinS.J., MarsonL., HowieS.E., et al.. The role of vascular endothelial growth factor in the kidney in health and disease. Nephron Physiol, 2004, 98(3): 73-79

[11] FengH.C., ChoyM.Y., DengW., et al.. Establishment and characterization of a human first-trimester extravillous trophoblast cell line (TEV-1). J Soc Gynecol Investig, 2005, 12: e21-e32

[12] SatchellS.C., TasmanC.H., SinghA., et al.. Conditionally immortalized human glomerular endothelial cells expressing fenestrations in response to VEGF. Kidney Int, 2006, 69(9): 1633-1640

[13] LivakK.J., SchmittgenT.D.. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 2001, 25(4): 402-408

[14] DuH., LiuH.Y., ZhaoJ., et al.. Effects of maternal serum on permeability of glomerular endothelial cell membrane. J Huazhong Univ Sci Technol [Med Sci], 2011, 31(1): 17-20

[15] ZhouQ., LiuH.Y., QiaoF.Y., et al.. VEGF deficit is involved in endothelium dysfunction in preeclampsia. J Huazhong Univ Sci Technol [Med Sci], 2010, 30(3): 370-374

[16] ZhouQ., QiaoF.Y., ZhaoC., et al.. Hypoxic trophoblast-derived sFlt-1 may contribute to endothelial dysfunction: an implication for the mechanism of trophoblast-endothelial dysfunction in preeclampsia. Cell Biol Int, 2011, 35(1): 61-66

[17] LeeuwisJ.W., NguyenT.Q., DendoovenA., et al.. Targeting podocyte-associated diseases. Adv Drug Deliv Rev, 2010, 62(14): 1325-1336

[18] LevineR.J., MaynardS.E., QianC., et al.. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med, 2004, 350(7): 672-683

[19] MaynardS.E., MinJ.Y., MerchanJ., et al.. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest, 2003, 111(5): 649-658

[20] LiZ., ZhangY., YingM. J., et al.. Recombinant vascular endothelial growth factor 121 attenuates hypertension and improves kidney damage in a rat model of preeclampsia. Hypertension, 2007, 50: 686-692