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Updated: May 26, 2025
Author Spotlight: Modeling an Aspect of Preeclampsia in Female Mice Using Hypoxic Human Placenta-Derived Small Extracellular Vesicles
Published on: January 26, 2024
Amniotic fluid-derived exosomal miR-146a-5p ameliorates preeclampsia phenotypes by inhibiting HIF-1α/FLT-1 expression
Jin Lin1, Xiaohong Huang2, Jing Zhang1
1Jiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China.
Introduction:
Preeclampsia (PE) is a pregnancy-specific complication that begins with hypertension and proteinuria and seriously threatens the health of pregnant women and fetuses. Abnormal expression of amniotic fluid-derived exosomal miR-146a-5p was observed in PE. However, the role of human amniotic fluid-derived exosomes (AF-Exos) and miR-146a-5p in PE remains unclear.
Methods:
We determined the miR-146a-5p expression pattern in the AF-Exos. AF-Exos, Cobalt chloride (CoCl2) and miR-146a-5p mimic were added to trophoblast cell lines HTR-8/SVneo and JEG-3, respectively. Then the proliferation and migration function of HTR-8/SVneo and JEG-3 cells were examined. The expression of miR-146a-5p, HIF-1α and FLT-1 in HTR-8/SVneo and JEG-3 cells were detected by RT-qPCR and western blotting. Finally, we determined the effect of AF-Exos in PE rat models.
Results:
MiR-146a-5p was down-regulated in AF-Exos of PE compared to normal. Co-cultured with normal AF-Exos significantly promoted proliferation and migration of HTR-8/SVneo and JEG-3 cells. CoCl2 inhibited proliferation and migration of HTR-8/SVneo and JEG-3 cells, while miR-146a-5p mimic reversed them by suppressing HIF-1α/FLT-1 expression. After treatment of AF-Exos, the blood pressure and 24-h urinary protein of PE rats were substantially decreased, the quality of fetuses and placenta exhibited improved, and HIF-1α/FLT-1 expression of placenta, sFlt-1 and sEng levels of blood, were substantial suppressed.
Conclusion:
The study provided experimental evidence for the protective effects of normal AF-Exos on ameliorating preeclampsia phenotypes, and miR-146a-5p may act an important role in enhancing the proliferation and migration of trophoblast cells by targeting HIF-1α.
