Amniotic fluid-derived exosomal miR-146a-5p ameliorates preeclampsia phenotypes by inhibiting HIF-1α/FLT-1 expression

Abstract

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.