Alleviation of preeclampsia-like symptoms through PlGF and eNOS regulation by hypoxia- and NF-κB-responsive miR-214-3p deletion

Abstract

Preeclampsia is caused by placental hypoxia and systemic inflammation and is associated with reduced placental growth factor (PlGF) and endothelial nitric oxide synthase (eNOS) levels. The molecular signaling axes involved in this process may play a role in the pathogenesis of preeclampsia. Here, we found that hypoxic exposure increased hypoxia-inducible factor-1α (HIF-1α)/Twist1-mediated miR-214-3p biogenesis in trophoblasts, suppressing PlGF production and trophoblast invasion. TNF-α stimulation increased NF-κB-dependent miR-214-3p expression in endothelial cells, impairing eNOS expression and causing endothelial dysfunction. Synthetic miR-214-3p administration to pregnant mice decreased PlGF and eNOS expression, resulting in preeclampsia-like symptoms, including hypertension, proteinuria, and fetal growth restriction. Conversely, miR-214-3p deletion maintained the PlGF and eNOS levels in hypoxic pregnant mice, alleviating preeclampsia-like symptoms and signs. These findings provide new insights into the role of HIF-1/Twist1- and NF-κB-responsive miR-214-3p-dependent PlGF and eNOS downregulation in the pathogenesis of preeclampsia and establish miR-214-3p as a therapeutic or preventive target for preeclampsia and its complications.

Hypoxia-induced miR-214-3p: key player in preeclampsia pathogenesis

This research investigates how a molecule, miR-214-3p, impacts the occurrence of preeclampsia - a pregnancy issue marked by high blood pressure and organ damage. Scientists discovered that miR-214-3p produced more when oxygen levels are low, suppresses two other molecules, PlGF and eNOS, essential for a healthy pregnancy. In mouse experiments, artificially increasing miR-214-3p led to preeclampsia-like symptoms, while mice without miR-214-3p alleviated these symptoms in low oxygen. This suggests miR-214-3p could be a focus for preeclampsia prevention or treatment. Further studies are required to confirm this. “This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.”