PDIA3 regulates trophoblast apoptosis and proliferation in preeclampsia via the MDM2/p53 pathway

in Reproduction
Authors:
Hui-Qin Mo Institute of Shanghai Key Laboratory of Embryo Original Diseases and Shanghai Municipal Key Clinical Specialty Project Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
The International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Fu-Ju Tian Institute of Shanghai Key Laboratory of Embryo Original Diseases and Shanghai Municipal Key Clinical Specialty Project Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
The International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Xiao-Ling Ma Institute of Shanghai Key Laboratory of Embryo Original Diseases and Shanghai Municipal Key Clinical Specialty Project Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
The International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Yu-Chen Zhang Institute of Shanghai Key Laboratory of Embryo Original Diseases and Shanghai Municipal Key Clinical Specialty Project Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
The International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Cheng-Xi Zhang Institute of Shanghai Key Laboratory of Embryo Original Diseases and Shanghai Municipal Key Clinical Specialty Project Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
The International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Wei-Hong Zeng Institute of Shanghai Key Laboratory of Embryo Original Diseases and Shanghai Municipal Key Clinical Specialty Project Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
The International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Yan Zhang Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China

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Yi Lin Institute of Shanghai Key Laboratory of Embryo Original Diseases and Shanghai Municipal Key Clinical Specialty Project Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
The International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Correspondence should be addressed to Y Lin; Email: yilinonline@126.com
DOI:
https://doi.org/10.1530/REP-20-0156
Volume/Issue:
Volume 160: Issue 2
Page Range:
293–305
Article Type:
Research Article
Online Publication Date:
Aug 2020
Copyright:
© 2020 Society for Reproduction and Fertility 2020
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Protein disulfide isomerase 3 (PDIA3) is a chaperone protein that modulates the folding of newly synthesized glycoproteins, has isomerase and redox activity, and has been implicated in the pathogenesis of many diseases. However, the role of PDIA3 in pregnancy-associated diseases remains largely unknown. Our present study reveals a key role for PDIA3 in the biology of placental trophoblasts from women with preeclampsia (PE). Immunohistochemistry and Western blot analysis revealed that PDIA3 expression was decreased in villous trophoblasts from women with PE compared to normotensive pregnancies. Further, using a Cell Counting Kit-8 assay, flow cytometry, and 5-ethynyl-2’-deoxyuridine (EdU) staining, we found that siRNA-mediated PDIA3 knockdown significantly promoted apoptosis and inhibited proliferation in the HTR8/SVneo cell line, while overexpression of PDIA3 reversed these effects. Furthermore, RNA sequencing and Western blot analysis demonstrated that knockdown of PDIA3 inhibited MDM2 protein expression in HTR8 cells, concurrent with marked elevation of p53 and p21 expression. Conversely, overexpression of PDIA3 had the opposite effects. Immunohistochemistry and Western blot further revealed that MDM2 protein expression was downregulated and p21 was increased in trophoblasts of women with PE compared to women with normotensive pregnancies. Our findings indicate that PDIA3 expression is decreased in the trophoblasts of women with PE, and decreased PDIA3 induces trophoblast apoptosis and represses trophoblast proliferation through regulating the MDM2/p53/p21 pathway.

Supplementary Materials

    • Table S1. Clinical characteristics of study pregnancies
    • Table S2. Primers used in RT-PCR assay detecting the mRNA levels of selected genes.
    • Table S3
    • Supplementary Figure S1
    • Supplementary Figure S2
    • Supplementary Data

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Print ISSN:
1470-1626
Online ISSN:
1741-7899

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