Role of sVEGFR (sFlt-1) in inducing endoplasmic reticulum stress in trophoblast cells and its status in preeclampsia

Abstract

IntroductionPreeclampsia (PE) and its subtypes (early and late onset) are serious concerns all across the globe affecting about 8% of overall pregnancies and accounts for approximately 60,000 deaths annually with a predominance in developing countries. The two-stage model, deficient spiral artery remodelling (stage I) and an imbalance between angiogenic and anti-angiogenic factor(s) (stage II) are well established facts so far. Increased sFlt-1 along with high oxidative stress and endoplasmic reticulum stress (ER stress) have recently been suggested in pregnancies with PE. The second decade of 21st century highlighted a new window to explore further the role of endoplasmic reticulum stress in the onset of the variant forms of PE. In our previous studies, we reported apoptosis and oxidative stress, induced by sFlt-1 in trophoblast cells. However, the role of sFlt-1 in inducing ER stress is still an unrevealed hugger-mugger till date. MethodsStudy was divided into two parts (1) Serum Analysis of sFlt-1 and GRP78 was done using ELISA (2) In Vitro experiments: Activation of ER stress markers (GRP78, eIF2α and CHOP) were assessed at various time points (8 h, 14 h, 24 h) at protein (Immunofluorescence, Western blot) and transcript level (qRT-PCR). ResultsSignificant raised levels of sFlt-1 and GRP78 in preeclamptic sera was found. We observed significant ER stress in the placental cells (BeWo Cells) (in vitro) when exposed to normotensive sera with recombinant sFlt-1 and also when treated with recombinant sFlt-1 alone. DiscussionWe reported significant ER stress in the placental cells (BeWo Cells) (in vitro) when exposed to normotensive sera with recombinant sFlt-1 and also when treated with recombinant sFlt-1 alone.