Human Umbilical Cord Mesenchymal Stem Cells-Derived Exosomal MicroRNA-18b-3p Inhibits the Occurrence of Preeclampsia by Targeting LEP

Qin Huang; Meng Gong; Tuantuan Tan; Yunong Lin; Yan Bao; Cuifang Fan

doi:10.1186/s11671-021-03475-5

Human Umbilical Cord Mesenchymal Stem Cells-Derived Exosomal MicroRNA-18b-3p Inhibits the Occurrence of Preeclampsia by Targeting LEP

Nanoscale Res Lett. 2021 Feb 10;16(1):27. doi: 10.1186/s11671-021-03475-5.

Authors

Qin Huang¹, Meng Gong¹, Tuantuan Tan², Yunong Lin³, Yan Bao¹, Cuifang Fan⁴

Affiliations

¹ Department of Obstetrics and Gynecology, Renmin Hosptial of Wuhan University, 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei, China.
² Ultrasound Imaging Department, Renmin Hosptial of Wuhan University, Wuhan, 430060, Hubei, China.
³ Department of Statistics, UW-Madison, Madison, 53703, USA.
⁴ Department of Obstetrics and Gynecology, Renmin Hosptial of Wuhan University, 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei, China. fancuifang@whu.edu.cn.

Abstract

Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) expressing microRNAs have been highlighted in human diseases. However, the detailed molecular mechanism of hucMSCs-derived exosomal miR-18b-3p on preeclampsia (PE) remains further investigation. We aimed to investigate the effect of exosomes and miR-18b-3p/leptin (LEP) on occurrence of PE. The morphology of the hucMSC and hucMSC-exosomes (Exos) was identified. The exosomes were infected with different lentivirus expressing miR-18b-3p to explore the role of miR-18b-3p in PE. The PE rat model was established by intraperitoneal injection of N-nitro-L-arginine methyl ester. The expression of LEP and miR-18b-3p was tested in PE rat placenta tissues. Also, the effect of exosomes on LEP and miR-18b-3p expression was detected. The systolic blood pressure (SBP), proteinuria, inflammatory factors, the weight of fetal rat and placenta and cell apoptosis in PE rats were detected. Finally, the relationship between miR-18b-3p and LEP was verified using dual-luciferase reporter gene assay and RNA pull-down assay. Exosomes, restoring miR-18b-3p or inhibiting LEP reduced SBP and proteinuria of PE rats as well as increased the weight of fetal rat and placenta, decreased serum levels of inflammatory factors as well as suppressed apoptotic cells of PE rats, exerting a suppressive effect on PE progression. miR-18b-3p was decreased and LEP was increased in placenta tissues of PE rats. LEP was the direct target gene of miR-18b-3p. Upregulation of miR-18b-3p or treatment of the exosomes suppressed LEP expression and reduced PE occurrence, while downregulation of miR-18b-3p had contrary effects. Downregulated LEP reversed the effect of miR-18b-3p reduction on PE rats. HucMSCs-derived exosomal miR-18b-3p targets LEP to participate in the occurrence and development of PE. This study may provide a novel theoretical basis for the mechanism and investigation of PE.

Keywords: Apoptosis; Exosomes; Human umbilical cord mesenchymal stem cells; Leptin; MicroRNA-18b-3p; Preeclampsia.

Publication types

Retracted Publication