ORIGINAL ARTICLE |
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Year : 2019 | Volume
: 68
| Issue : 3 | Page : 187-195 |
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Vascular endothelial growth factor alleviates endoplasmic reticulum stress via PERK, IRE1, and ATF6 pathways in trophoblast cells
Sankat Mochan1, Manoj K Dhingra2, Sunil K Gupta1, Shobhit Saxena1, Pallavi Arora1, Neerja Rani1, Neerja Bhatla3, Sada Nand Dwivedi4, Renu Dhingra1
1 Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India 2 Department of Community Medicine, NC Medical College and Hospital, Panipat, Haryana, India 3 Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India 4 Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
Correspondence Address:
Prof. Renu Dhingra Department of Anatomy, All India Institute of Medical Sciences, New Delhi - 110 029 India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/JASI.JASI_143_19
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Introduction: In developing countries, preeclampsia is still a leading cause of maternal mortality and morbidity, affecting nearly 8%–10% of pregnancies and overall death. Apart from various stresses that placenta undergoes while pregnancy, endoplasmic reticulum (ER) stress has been the center of attraction for several researchers all across the globe. Imbalance in circulating pro- and anti-angiogenic agents in maternal serum has also been linked with the upregulation of stress at subcellular level. The present study is an attempt to demonstrate the role of pro-angiogenic factor in mitigating ER stress in trophoblast cells. Material and Methods: Evaluation of expression of ER stress markers (eIF2α, X-box binding protein-1, and ATF6) at various time points was done after exposure of varying concentration (s) of pro-angiogenic factor (from preeclamptic mothers) to trophoblast cells (BeWo cells). Expression was also analyzed when BeWo cells were exposed to recombinant vascular endothelial growth factor (VEGF) along with serum from preeclamptic mothers. Molecular techniques used were immunofluorescence staining and Western blot analysis. Results: Immunofluorescence staining and Western blot analysis demonstrated upregulated expression of studied ER stress markers in BeWo cells when they were exposed to Preeclampsia (PE) sera. Exogenous addition of recombinant VEGF along with preeclamptic sera significantly reduced the expression of ER stress markers. Discussion and Conclusion: In the present study, significantly reduced expression of ER stress markers in BeWo cells indicates an interrelationship of angiogenic factor and molecular transmembrane sensors. Further experimentations thus may provide a strong base for the modulation of ER stress sensors, which could be effective in minimizing ER stress in preeclamptic pregnancies and thus would bring a new hope to numerous women worldwide.
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