VEGF-A regulates sFlt-1 production in trophoblasts through both Flt-1 and KDR receptors

Molecular and Cellular Biochemistry
Zhonglin XiaoXiujun Fan

Abstract

Studies have shown that sFlt-1 overproduction stimulated by excess VEGF of deciduous origin in trophoblasts can cause preeclampsia. However, the mechanism underlying how VEGF regulates sFtl-1 expression in trophoblasts remains unknown. To address this issue, JEG3 and HTR-8/SV neo (HTR8) trophoblast cell lines were used to investigate the signaling pathways involved in the regulation of sFlt-1 production via VEGF overexpression in vitro. JEG3 (VEGF-GFP-JEG3, V-J) and HTR8 (VEGF-GFP-HTR8, V-H) cells overexpressing VEGF165 were established by infecting the JEG3 and HTR8 cell lines with lentivirus expressing VEGF165. Both the mRNA and protein levels of VEGF and sFlt-1 were dramatically up-regulated in the V-J and V-H cells compared to the JEG3 and HTR8 cells, and they were significantly decreased after treatment with an Flt-1 receptor inhibitor (MK-2461), a KDR receptor inhibitor (XL-184), or an Flt-1 and KDR receptor inhibitor (ABT-869). The mRNA levels of sFlt-1, Flt-1, and KDR were increased in V-H cells after treatment, and the VEGF-A mRNA levels were also elevated. The migration and invasion abilities of JEG3 and HTR8 cells were decreased after VEGF overexpression, and this reduction could be reversed with VEGF receptor inhibi...Continue Reading

References

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Citations

Apr 9, 2020·International Journal of Molecular Sciences·Miguel A OrtegaNatalio García-Honduvilla
Dec 19, 2019·American Journal of Physiology. Cell Physiology·Zhilong ChenQing Yang
Jul 1, 2020·Biomolecules·Manoj Kumar JenaNihar Ranjan Nayak
Jan 19, 2022·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Giuseppe BroggiFelice Giangaspero

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Methods Mentioned

BETA
enzyme-linked immunosorbent assays
PCR
scraping
flow cytometry
transfection
ELISA

Software Mentioned

GraphPad Prism
ImageJ

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