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QSOX1 regulates trophoblastic apoptosis in preeclampsia through hydrogen peroxide production.

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journal contribution
posted on 25.05.2018, 11:26 by Jinjin Li, Chao Tong, Ping Xu, Lianlian Wang, Ting-li Han, Li Wen, Xiaofang Luo, Bin Tan, Fangyu Zhu, Shunping Gui, Rufei Gao, Hongbo Qi, Philip N. Baker
OBJECTIVE: Oxidative stress plays a significant role in the pathogenesis of preeclampsia (PE), by inducing trophoblast cell death and consequent placental dysfunction. Quiescin sulfhydryl oxidase 1 (QSOX1) is upregulated in many types of cancer cells; it promotes disulfide bond formation as well as hydrogen peroxide (H2O2) production. The aims of present study are to investigate the expression pattern of QSOX1 in placentae of pregnancies complicated by PE and the role of QSOX1 in the regulation of trophoblastic function, thus providing in-depth understanding of the putative involvement of QSOX1 in the development of PE. METHODS: Human term placenta from normal pregnancies and from pregnancies complicated by PE were collected to measure QSOX1 expression and H2O2 levels. Down-regulation of QSOX1 in HTR-8/Svneo cells was achieved by siRNA interference. An in vitro cellular PE model was generated by hypoxic incubation. Protein expression levels were assessed by Western blotting, and H2O2 levels were determined in the cell culture medium as well as in the cell lysate. Trophoblast apoptosis was evaluated by TUNEL staining. RESULTS: QSOX1 was overexpressed in the PE placenta. Inhibition of QSOX1 expression in HTR-8/Svneo cells attenuated cell apoptosis and intracellular H2O2 levels. Hypoxia induced QSOX1 expression in HTR-8/Svneo cells and led to apoptosis of HTR-8/Svneo cells, and knock-down of QSOX1 rescued hypoxia induced trophoblast apoptosis. CONCLUSIONS: Hypoxia induced up-regulation of QSOX1 and a consequent elevation in intracellular H2O2 increased apoptosis in placentae of pregnancies complicated by PE.

Funding

This work was supported by grants from the National Natural Sciences Foundation of China (81520108013 to H.Q; 81671488 to C.T, 81701479 to F.Z, 81701480 to S.G), Ministry of Science and Technology of China (2016YFC1000407 to H.Q), Chongqing Municipal Education Commission (CXTDX201601014 to H.Q), Commission of Science and Technology of Chongqing Municipality (cstc2017jcyjBX0045 to C.T). In addition, this study was supported by the “111 program” of Ministry of Education P.R.C and State Administration of Foreign Experts Affairs P.R.C, and State International Collaborative Laboratory of Reproduction and Development.

History

Citation

Journal of Maternal-Fetal and Neonatal Medicine, 2018

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES

Version

AM (Accepted Manuscript)

Published in

Journal of Maternal-Fetal and Neonatal Medicine

Publisher

Taylor & Francis for European Association of Perinatal Medicine, Federation of Asia and Oceania Perinatal Societies, Ibero-American Society for Prenatal Diagnosis and Therapy, International Society of Perinatal Obstetrician

issn

1476-7058

eissn

1476-4954

Acceptance date

27/04/2018

Copyright date

2018

Available date

30/04/2019

Publisher version

https://www.tandfonline.com/doi/abs/10.1080/14767058.2018.1471459

Notes

The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.

Language

en

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