Alleviation of preeclampsia-like symptoms through PlGF and eNOS regulation by hypoxia- and NF-κB-responsive miR-214-3p deletion.
Suji KimSungbo ShimJisoo KwonSungwoo RyooJunyoung ByeonJungwoo HongJeong-Hyung LeeYoung-Guen KwonJi-Yoon KimYoung-Myeong KimPublished in: Experimental & molecular medicine (2024)
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.
Keyphrases
- endothelial cells
- nitric oxide synthase
- early onset
- pi k akt
- signaling pathway
- nitric oxide
- poor prognosis
- growth factor
- pregnancy outcomes
- high glucose
- epithelial mesenchymal transition
- pregnant women
- cell proliferation
- vascular endothelial growth factor
- oxidative stress
- lps induced
- rheumatoid arthritis
- sleep quality
- nuclear factor
- cancer therapy
- long non coding rna
- high fat diet induced
- risk factors
- binding protein
- drug delivery
- skeletal muscle
- depressive symptoms