MiR-142-5p mediated Nrf2 dysregulation in gestational diabetes mellitus and its impact on placental angiogenesis
Gestational diabetes mellitus (GDM) presents significant risks during pregnancy, including adverse perinatal outcomes and placental dysfunction. Impaired angiogenesis, involving crucial factors like Vascular Endothelial Growth Factor (VEGF), contributes to these complications. The Nrf2/Keap1 pathway...
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Published in | Placenta (Eastbourne) Vol. 158; pp. 192 - 199 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Ltd
01.12.2024
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Subjects | |
Online Access | Get full text |
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Summary: | Gestational diabetes mellitus (GDM) presents significant risks during pregnancy, including adverse perinatal outcomes and placental dysfunction. Impaired angiogenesis, involving crucial factors like Vascular Endothelial Growth Factor (VEGF), contributes to these complications. The Nrf2/Keap1 pathway, crucial for vascular redox homeostasis, has been linked to GDM-associated angiogenesis dysregulation.
This study aimed to investigate the molecular mechanisms underlying placental Nrf2 regulation, focusing on angiomiRs, key regulators of angiogenesis in GDM. Computational analysis identified miR-142-5p targeting Nrf2 mRNA. Expression levels of miR-142-5p were assessed in GDM placenta and correlated with Nrf2 expression. Experimental validation utilized human trophoblastic cell lines (BeWo) exposed to hyperglycemic conditions, assessing the effects of anti-miR-142 transfection on Nrf2 expression and angiogenic marker levels.
miR-142-5p expression was significantly downregulated in GDM placenta, correlating positively with Nrf2 expression. In BeWo cells exposed to hyperglycemia, anti-miR-142 transfection notably increased Nrf2 expression alongside angiogenic marker levels, confirming the computational predictions.
Our findings highlight the pivotal role of miRNAs in GDM-associated impaired angiogenesis by modulating Nrf2 expression. Understanding these molecular mechanisms provides insights into potential therapeutic targets for improving pregnancy outcomes in GDM cases.
•Nrf2, its downstream targets and angiogenic factors were downregulated in GDM placenta.•Overexpression of miR-142-5p impairs angiogenesis via dysregulation of Nrf2 in GDM.•MiR-142-5p directly binding with functional domains of Nrf2 in silico.•Silencing miR-142-5p restores Nrf2 and angiogenesis expression in HG induced BeWo cells. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0143-4004 1532-3102 1532-3102 |
DOI: | 10.1016/j.placenta.2024.10.021 |