Increased trophoblast expression of NFAT5/TonEBP in pre-eclamptic placentas and hyperosmolar-treated BeWo cells

Abstract

Objectives: To assess the concentrations of inositol and sorbitol, and determine the expression of related osmolyte factors [nuclear factor of activated T cells 5, also known as tonicity responsive binding protein (NFAT5/TonEBP); sodium myo-inositol transporter (SLC5A3); and aldose reductase] in placentas of pre-eclamptic (PE) patients and trophoblast BeWo cells subjected to hypertonic stress in vitro.

Study design: Control and PE placentas were collected. BeWo cells were cultured and subjected to a hyperosmolar solution for 4h. Western blot analysis was performed on NFAT5, SLC5A3, aldose reductase and ERK proteins. High-performance liquid chromatography was used to determine the levels of inositol and sorbitol in cell lysates.

Results: Compared with control placentas, PE placentas showed higher levels of inositol and NFAT5, and lower levels of SLC5A3. Treated BeWo cells showed higher levels of inositol, sorbitol, NFAT5 total protein, SLC5A3 and aldose reductase, and increased ERK activation compared with control BeWo cells.

Conclusions: Hyperosmolar conditions increase the expression of NFAT5 in PE placentas and BeWo cells, and may account for the increased osmolyte levels. NFAT5 may accomplish this through aldose reductase and SLC5A3 in trophoblast cells.

Keywords: Inositol; NFAT5/TonEBP; Pre-eclampsia; Sorbitol; Trophoblast.