Department of Obstetrics, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA.
Cells. 2022 Nov 1;11(21):3457. doi: 10.3390/cells11213457.
Gestational diabetes mellitus (GDM) leads to poor pregnancy outcomes and fetoplacental endothelial dysfunction; however, the underlying mechanisms remain unknown. This study aimed to investigate the effect of placenta-derived exosomal miRNAs on fetoplacental endothelial dysfunction in GDM, as well as to further explore the role of chemerin to this end. Placenta-derived exosomal miR-140-3p and miR-574-3p expression (next-generation sequencing, quantitative real-time PCR), its interactions with cell function (Cell Counting Kit-8, Transwell, tube formation assay), chemerin interactions (Western blotting), and placental inflammation (immunofluorescence staining, enzyme-linked immunosorbent assay) were investigated. Placenta-derived exosomal miR-140-3p and miR-574-3p were downregulated in GDM. Additionally, miR-140-3p and miR-574-3p inhibited the proliferation, migration, and tube formation ability of umbilical vein endothelial cells by targeting vascular endothelial growth factor. Interestingly, miR-140-3p and miR-574-3p expression levels were negatively correlated with chemerin, which induced placental inflammation through the recruitment of macrophage cells and release of IL-18 and IL-1β. These findings indicate that chemerin reduces placenta-derived exosomal miR-140-3p and miR-574-3p levels by inducing placental inflammation, thereby promoting the proliferation, migration, and tube formation of umbilical vein endothelial cells in GDM, providing a novel perspective on the underlying pathogenesis and therapeutic targets for GDM and its offspring complications.
妊娠期糖尿病（GDM）可导致妊娠结局不良和胎盘中皮功能障碍，但具体的发病机制尚不清楚。本研究旨在探讨胎盘来源的外泌体 miRNA 对 GDM 胎盘中皮功能障碍的影响，并进一步探讨 chemerin 在其中的作用。通过下一代测序、实时定量 PCR 检测胎盘来源的外泌体 miR-140-3p 和 miR-574-3p 的表达；通过细胞计数试剂盒-8（Cell Counting Kit-8）、Transwell、管形成试验检测其与细胞功能的相互作用；通过 Western blot 检测 chemerin 的相互作用；通过免疫荧光染色、酶联免疫吸附试验检测胎盘炎症。GDM 患者的胎盘来源外泌体 miR-140-3p 和 miR-574-3p 表达下调。此外，miR-140-3p 和 miR-574-3p 通过靶向血管内皮生长因子抑制脐静脉内皮细胞的增殖、迁移和管形成能力。有趣的是，miR-140-3p 和 miR-574-3p 的表达水平与 chemerin 呈负相关，chemerin 通过募集巨噬细胞细胞并释放白细胞介素-18（IL-18）和白细胞介素-1β（IL-1β）诱导胎盘炎症。这些发现表明，chemerin 通过诱导胎盘炎症降低胎盘来源的外泌体 miR-140-3p 和 miR-574-3p 水平，从而促进 GDM 中脐静脉内皮细胞的增殖、迁移和管形成，为 GDM 及其后代并发症的发病机制和治疗靶点提供了新的视角。
