Pregnancy-Specific Glycoprotein 9 Enhances Store-Operated Calcium Entry and Nitric Oxide Release in Human Umbilical Vein Endothelial Cells

Diagnostics · 10 authors, 5 centres

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TL;DR

This study measured serum PSG9 levels in pregnant women with preeclampsia versus healthy pregnant women and performed in vitro experiments on HUVECs treated with PSG9. Pregnant women with preeclampsia had significantly lower serum PSG9 levels, and PSG9 at 0.1 μg/mL enhanced SOCE-mediated calcium influx, eNOS expression, and NO release in HUVECs via Orai1 and Orai2.

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Serum PSG9 levels were significantly lower in women with preeclampsia. Application of PSG9 at 0.1 μg/mL to HUVECs increased expression of Orai1 and Orai2, promoting SOCE-mediated Ca2+ influx and enhancing eNOS expression and NO production. BTP2, an Orai channel inhibitor, blocked PSG9-induced eNOS expression and NO production. A higher PSG9 concentration (0.5 μg/mL) did not increase eNOS expression, suggesting dose-dependent effects.

STUDY TYPE

other

SPECIALTY

obstetrics and gynecology

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AI pipeline

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100% · A

ORIGINAL PAPER

PMC10047280

Pregnancy-Specific Glycoprotein 9 Enhances Store-Operated Calcium Entry and Nitric Oxide Release in Human Umbilical Vein Endothelial Cells

Diagnostics

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ABSTRACT

Abstract We explored changes in pregnancy-specific glycoprotein 9 (PSG9) levels in the serum of patients with preeclampsia and the effects and underlying mechanisms of PSG9 effects on calcium (Ca 2+ ) homeostasis and nitric oxide (NO) release in human umbilical vein endothelial cells (HUVECs). Western blotting was used to detect protein expression levels, and an NO fluorescence probe was used to examine NO production. Intracellular Ca 2+ concentrations were measured using a Ca 2+ -sensitive fluorescent dye under a fluorescence microscope. Compared with those in healthy pregnant women, serum PSG9 levels were significantly decreased in patients with preeclampsia. PSG9 (0.1 μg/mL) treatment of HUVECs significantly enhanced the expression levels of store-operated calcium entry (SOCE) channel proteins Orai1 and Orai2, but not Orai3, and of endothelial nitric oxide synthase (eNOS) and NO production. Pretreatment with an inhibitor of SOCE (BTP2) abolished PSG9-enhanced Orai1, Orai2, and eNOS expression levels and NO production in HUVECs. The mechanisms underlying SOCE that were PSG9 enhanced in HUVECs appear to involve the Ca 2+ /eNOS/NO signaling pathway. These findings suggest that serum PSG9 levels may be a potential biomarker for monitoring the occurrence or development of preeclampsia in pregnancy and that PSG9 may be a potential therapeutic target for the treatment of preeclampsia. Keywords: preeclampsia, pregnancy-specific glycoprotein 9, endothelial function, nitric oxide synthase, calcium store manipulates calcium influx

CITATION EXPORT

Ying Qin, Qinggang Meng, Qunhua Wang et al.. Pregnancy-Specific Glycoprotein 9 Enhances Store-Operated Calcium Entry and Nitric Oxide Release in Human Umbilical Vein Endothelial Cells. Diagnostics. (2023). https://doi.org/10.3390/diagnostics13061134

AUTHORS

10 · 5 CENTRES

Ying Qin, Qinggang Meng, Qunhua Wang, Mingzhu Wu, Yan Fang, Chengcheng Tu, Xinyang Hu, Bing Shen, Hongbo Chen, Xiaohong Xu

1Clinical Laboratory, Anhui No. 2 Provincial People’s Hospital, Hefei 230011, China; [email protected]
2School of Basic Medicine, Anhui Medical University, Hefei 230032, China; [email protected] (X.H.); [email protected] (B.S.)
3Department of Obstetrics and Gynecology, Maternal and Child Health Hospital, The Affiliated Hospital of Anhui Medical University, Hefei 230032, China; [email protected] (Q.M.); [email protected] (M.W.); [email protected] (Y.F.); [email protected] (C.T.)
4Department of Obstetrics and Gynecology, The Fist Affiliated Hospital of USTC, Anhui Provincial Hospital, Hefei 230032, China; [email protected]
5Department of Clinical Laboratory, Maternal and Child Health Hospital, The Affiliated Hospital of Anhui Medical University, Hefei 230032, China