METTL3 promotes trophoblast ferroptosis in preeclampsia by stabilizing the ACSL4 m6A modification
Copyright © 2024 Elsevier Inc. All rights reserved..
This study aims to explore the role of methyltransferase-like 3 (METTL3) modulation of ferroptosis in the pathogenesis of trophoblast-mediated preeclampsia. The expression of METTL3 and acyl-CoA synthetase long chain family member 4 (ACSL4) was measured in clinical placental tissues and trophoblasts using qPCR and Western blot techniques. The effects of METTL3 on the symptoms of preeclampsia were also validated in rat models. METTL3 and ACSL4 were upregulated in placental tissues from patients with preeclampsia and in hypoxia-induced trophoblasts. METTL3 silencing increased the migration and invasion of trophoblasts cultured under hypoxic conditions. Knockdown of METTL3 increased cell viability and suppressed ferroptosis in hypoxia-stimulated trophoblasts. Hypoxia increased the level of m6A in cells, whereas silencing METTL3 partially reversed this change. Silencing METTL3 resulted in a decrease in m6A modification of ACSL4 mRNA, which led to a reduction in ACSL4 mRNA stability. ACSL4 upregulation partially reversed the effects of METTL3 silencing on cell viability, migration, invasion, and ferroptosis in hypoxia-stimulated trophoblasts. Inhibition of METTL3 in preeclampsia rats decreased blood pressure, urine protein levels, fetal survival rate, and ACSL4-mediated ferroptosis. METTL3 elevates ferroptosis to inhibit the migration and invasion of trophoblasts and in vivo preeclampsia symptoms by catalyzing the m6A modification of ACSL4 mRNA.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:437 |
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| Enthalten in: |
Experimental cell research - 437(2024), 1 vom: 01. Apr., Seite 113990 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Yang [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.04.2024 Date Revised 10.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.yexcr.2024.113990 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a METTL3 promotes trophoblast ferroptosis in preeclampsia by stabilizing the ACSL4 m6A modification |
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| 520 | |a This study aims to explore the role of methyltransferase-like 3 (METTL3) modulation of ferroptosis in the pathogenesis of trophoblast-mediated preeclampsia. The expression of METTL3 and acyl-CoA synthetase long chain family member 4 (ACSL4) was measured in clinical placental tissues and trophoblasts using qPCR and Western blot techniques. The effects of METTL3 on the symptoms of preeclampsia were also validated in rat models. METTL3 and ACSL4 were upregulated in placental tissues from patients with preeclampsia and in hypoxia-induced trophoblasts. METTL3 silencing increased the migration and invasion of trophoblasts cultured under hypoxic conditions. Knockdown of METTL3 increased cell viability and suppressed ferroptosis in hypoxia-stimulated trophoblasts. Hypoxia increased the level of m6A in cells, whereas silencing METTL3 partially reversed this change. Silencing METTL3 resulted in a decrease in m6A modification of ACSL4 mRNA, which led to a reduction in ACSL4 mRNA stability. ACSL4 upregulation partially reversed the effects of METTL3 silencing on cell viability, migration, invasion, and ferroptosis in hypoxia-stimulated trophoblasts. Inhibition of METTL3 in preeclampsia rats decreased blood pressure, urine protein levels, fetal survival rate, and ACSL4-mediated ferroptosis. METTL3 elevates ferroptosis to inhibit the migration and invasion of trophoblasts and in vivo preeclampsia symptoms by catalyzing the m6A modification of ACSL4 mRNA | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Ferroptosis | |
| 650 | 4 | |a Methyltransferase-like 3 | |
| 650 | 4 | |a N(6)-methyladenosine | |
| 650 | 4 | |a Preeclampsia | |
| 650 | 4 | |a Trophoblasts | |
| 650 | 7 | |a Methyltransferases |2 NLM | |
| 650 | 7 | |a EC 2.1.1.- |2 NLM | |
| 650 | 7 | |a METTL3 protein, human |2 NLM | |
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| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a Acsl4 protein, rat |2 NLM | |
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| 650 | 7 | |a long-chain-fatty-acid-CoA ligase |2 NLM | |
| 650 | 7 | |a EC 6.2.1.3 |2 NLM | |
| 650 | 7 | |a Mettl3 protein, rat |2 NLM | |
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| 700 | 1 | |a Zhang, Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xuemei |e verfasserin |4 aut | |
| 700 | 1 | |a Qi, Hongbo |e verfasserin |4 aut | |
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