Biology subjects

Dwivedi, S. N.

Publications and source records attributed to Dwivedi, S. N..

2 recordsLinked to original sources

bioRxiv2023

Upregulated GRP78 and sFlt-1 in preeclampsia induces IRE1 and ATF6 arms of UPR leading to ER stress in placental cells

IntroductionAmongst vivid and diversified stresses which placenta in preeclampsia undergoes, ER stress has been a hal of the fame which is an insinuation of ill-fated UPR. In our previous study, we have already reported activation of PERK arm due to sFlt-1 present in preeclamptic mothers. The present study is an attempt to interpret rest of the two arms (IRE1 and ATF6) of UPR and ER stress subsequently by in vitro study using BeWo cells after upregulation of master regulator of UPR (GRP78) in placental tissue. Materials and MethodsPart I: Serum analysis of circulating levels of GRP78 and sFlt-1 [in 50 pairs of preeclamptic and normotensive, non-proteinuric (control) pregnant women)] using ELISA. Part II: Correlation analysis of levels of GRP78 and sFlt-1 in preeclamptic and control groups. Part III: Status of expression of GRP78 in placentae (n=10 each, preeclamptic and control groups) was reported using immunofluorescence. Part IV: In vitro experiments using BeWo cells were carried out to analyse the effect of GRP78 and sFlt-1 on IRE1 and ATF6 arms of UPR at protein (immunofluorescence and western blot) and transcript (qRT-PCR) levels. ResultsProtein expressions of GRP78 and sFlt-1 were found significantly elevated in preeclamptic patients as compared to controls. Enhanced expression of master regulator of UPR (GRP78) in placental tissue of preeclamptic women was reported. Up-regulated expression of XBP1 (IRE1 arm) and ATF6 markers of UPR was observed in trophoblast cells. ConclusionThe upregulated expression of GRP78 in preeclamptic placentae and enhanced expression of XBP1 and ATF6 markers in BeWo cells at both protein and transcript levels connote role played by raised circulating levels of GRP78 and sFlt-1 in preeclampsia.

developmental biology↗

bioRxiv2018

sFlt-1 commutes unfolded protein response into endoplasmic reticulum stress in trophoblast cells in preeclamptic pregnancies

Preeclampsia (PE) and its subtypes (early and late onset) are serious concerns all across the globe affecting about 8% of total pregnancies and accounts for approximately 60,000 deaths annually with a predominance in developing under-developed and countries. The two-stage model in the progression of this disease, deficient spiral artery remodelling and an imbalance between angiogenic (VEGF) and anti-antigenic factor(s) (sFlt-1) are well established facts pertaining to this disease. The presence of increased sFlt-1, high oxidative stress and Endoplasmic reticulum stress (ER stress) have been proposed in preeclamptic pregnancies. Recently, the role of endoplasmic reticulum stress in the onset of the variant forms of PE highlighted a new window to explore further. In our previous studies, we demonstrated that sFlt-1 can induce apoptosis and oxidative stress in trophoblast cells. However the role of sFlt-1, in inducing ER stress is not known so far. In the present study, we for the first time demonstrated significant ER stress in the placental cells (BeWo Cells) (in vitro) when exposed to sera from preeclamptic pregnancies having increased concentration of sFlt-1. The expression of ER stress markers (GRP78, eIF2, XBP1, ATF6 and CHOP) at both transcript and protein levels were compared (between preeclamptic and normotensive non-proteinuric women) at three different time points (8h, 14h and 24hrs), analyzed and found to be significant (p<0.05).\n\nConclusionOur results suggested that sFlt-1, released from placental cells in preeclampsia may be one of the various factors having potential to induce endoplasmic reticulum stress in BeWo cells.

developmental biology↗