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Published on: January 20, 2019
PABPC1 regulates EOPE pathogenesis through modulating TMBIM4 mRNA expression and stability
Shuyu Zhao1, Nan Lv1, Tianyi Liu1
1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, No. 246, Xuefu Road, Harbin, 150001, China.
Poly(A) Binding Protein Cytoplasmic 1 (PABPC1) suppresses early-onset preeclampsia (EOPE) by enhancing trophoblast cell proliferation and invasion. PABPC1 increases the stability of Transmembrane BAX Inhibitor Motif Containing 4 (TMBIM4) mRNA, offering a potential therapeutic strategy for EOPE.
Area of Science:
- Obstetrics and Gynecology
- Molecular Biology
- Cell Biology
Background:
- Preeclampsia (PE) is a severe pregnancy complication linked to inadequate trophoblast cell function.
- Transmembrane BAX Inhibitor Motif Containing 4 (TMBIM4) is downregulated in early-onset preeclampsia (EOPE) placental tissues.
- Poly(A) Binding Protein Cytoplasmic 1 (PABPC1) regulates mRNA stability and cell behavior.
Purpose of the Study:
- To investigate the role of PABPC1 in trophoblast cell proliferation and invasion.
- To determine how PABPC1 affects TMBIM4 mRNA stability.
- To explore PABPC1 as a potential therapeutic target for EOPE.
Main Methods:
- In vitro studies using HTR-8/SVneo cells with PABPC1 manipulation.
- In vivo studies using a rat model of preeclampsia.
- RIP-qPCR and dual luciferase reporter assays to confirm PABPC1-TMBIM4 interaction.
Main Results:
- PABPC1 overexpression promoted trophoblast cell proliferation, migration, and invasion while inhibiting apoptosis.
- PABPC1 upregulation ameliorated hypertension and kidney damage in a rat model.
- PABPC1 enhances TMBIM4 mRNA stability by binding to its 3'UTR, and TMBIM4 is crucial for PABPC1's effects.
Conclusions:
- PABPC1 suppresses EOPE by enhancing trophoblast proliferation and invasion via increased TMBIM4 mRNA stability.
- PABPC1 plays a critical role in EOPE pathogenesis.
- PABPC1 upregulation presents a promising therapeutic strategy for EOPE.
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