Huang Qin, Gong Meng, Tan Tuantuan, Lin Yunong, Bao Yan, Fan Cuifang
Department of Obstetrics and Gynecology, Renmin Hosptial of Wuhan University, 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei, China.
Ultrasound Imaging Department, Renmin Hosptial of Wuhan University, Wuhan, 430060, Hubei, China.
Nanoscale Res Lett. 2021 Feb 10;16(1):27. doi: 10.1186/s11671-021-03475-5.
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.
表达微小RNA的人脐带间充质干细胞（hucMSCs）来源的外泌体在人类疾病中受到关注。然而，hucMSCs来源的外泌体miR-18b-3p在子痫前期（PE）中的详细分子机制仍有待进一步研究。我们旨在研究外泌体和miR-18b-3p/瘦素（LEP）对PE发生的影响。鉴定了hucMSC和hucMSC-外泌体（Exos）的形态。用表达miR-18b-3p的不同慢病毒感染外泌体，以探讨miR-18b-3p在PE中的作用。通过腹腔注射N-硝基-L-精氨酸甲酯建立PE大鼠模型。检测PE大鼠胎盘组织中LEP和miR-18b-3p的表达。此外，检测外泌体对LEP和miR-18b-3p表达的影响。检测PE大鼠的收缩压（SBP）、蛋白尿、炎症因子、胎鼠和胎盘重量以及细胞凋亡情况。最后，使用双荧光素酶报告基因测定法和RNA下拉测定法验证miR-18b-3p与LEP之间的关系。外泌体、恢复miR-18b-3p或抑制LEP可降低PE大鼠的SBP和蛋白尿，增加胎鼠和胎盘重量，降低血清炎症因子水平，并抑制PE大鼠的凋亡细胞，对PE进展发挥抑制作用。PE大鼠胎盘组织中miR-18b-3p降低而LEP升高。LEP是miR-18b-3p的直接靶基因。上调miR-18b--3p或用外泌体处理可抑制LEP表达并减少PE的发生，而下调miR-18b-3p则有相反作用。下调LEP可逆转miR-18b-3p降低对PE大鼠的影响。hucMSCs来源的外泌体miR-18b-3p靶向LEP参与PE的发生和发展。本研究可能为PE的机制和研究提供新的理论依据。
