2. Academic Validation
  3. ZFP36 inhibits trophoblast ferroptosis and attenuates preeclampsia development by promoting NCOA4 mRNA degradation and suppressing ferritinophagy

ZFP36 inhibits trophoblast ferroptosis and attenuates preeclampsia development by promoting NCOA4 mRNA degradation and suppressing ferritinophagy

  • Biochem Pharmacol. 2026 Jun:248:117836. doi: 10.1016/j.bcp.2026.117836.
Man Gao 1,  Xue Yang 2,  Xiuxia Wang 3,  Tong Liu 4
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
  • 2 Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China.
  • 3 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China. Electronic address: [email protected].
  • 4 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China. Electronic address: [email protected].
PMID: 41765113 DOI: 10.1016/j.bcp.2026.117836
Abstract

Preeclampsia (PE), a pregnancy-specific disorder characterized by placental dysfunction and severe maternal-fetal complications, involves ferroptosis-an iron-dependent cell death driven by oxidative stress and lipid peroxidation. This study investigated the role of zinc-finger protein 36 (ZFP36) in regulating Ferroptosis in trophoblast cells and its underlying mechanisms.In vitro, hypoxia/reoxygenation was applied to human trophoblast HTR-8/SVneo cells to model ischemic injury. ZFP36 was found to inhibit oxidative stress and Ferroptosis by suppressing nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy. Mechanistically, ZFP36 binds to the 3' untranslated regions (3'UTRs) ofNCOA4mRNA, promoting its degradation and thereby attenuating ferritinophagy.In vivo, lentiviral overexpression of ZFP36 in a rat model of PE (induced by reduced uteroplacental perfusion pressure) alleviated clinical symptoms and reduced NCOA4-mediated Ferroptosis. Collectively, these results demonstrate that ZFP36 regulates Ferroptosis by modulating NCOA4-dependent ferritinophagy, offering a potential therapeutic strategy for PE through targeting Ferroptosis.

Keywords

Ferroptosis; Preeclampsia; Trophoblast cells; ZFP36.

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