Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, People's Republic of China.
Acta Diabetol. 2022 Aug;59(8):1091-1107. doi: 10.1007/s00592-022-01910-2. Epub 2022 Jun 8.
The aim of this study was to investigate the roles of miR-130b-3p and ICAM-1 in gestational diabetes mellitus (GDM) and their potential association.
Human placenta mesenchymal stem cells (PlaMSCs) were isolated from GDM patients, and the effects of the PlaMSCs from GDM patients (GDM-MSCs) and the exosomes secreted by GDM-MSCs on human umbilical vein endothelial cell (HUVEC) proliferation, migration, and angiogenesis were detected. Next, GDM-MSCs were transfected with miR-130b-3p antagomir to modify miR-130b-3p expression in GDM-MSCs-derived exosomes, and the exosomes with modified miR-130b-3p expression were cultured with HUVECs to evaluate exosomal miR-130b-3p on HUVEC function. Furthermore, a target gene of miR-130b-3p was predicted and assessed. The miR-130b-3p-modified exosomes were cultured with HUVECs transfected with ICAM-1 shRNA to determine the effect of miR-130b-3p-ICAM-1 crosstalk on HUVEC function. Additionally, a GDM mouse model was conducted to further study the effect of miR-130b-3p in GDM in vivo.
GDM-MSCs inhibited HUVEC proliferation and angiogenesis. The elevated expression of miR-130b-3p was found in GDM-MSCs-derived exosomes. GDM-MSCs-derived exosomes repressed the proliferation and angiogenesis of HUVECs and miR-130b-3p inhibition could restrain the inhibition of the exosomes on HUVEC function. Mechanistically, miR-130b-3p downregulated ICAM-1 expression in a targeted manner, and thereby enhanced HUVEC proliferation, migration, and angiogenesis and increased the expression of angiogenesis-related factors. Moreover, miR-130b-3p inhibition promoted placental angiogenesis in GDM mice and upregulated ICAM-1 expression.
Conclusively, GDM-MSCs-derived exosomes shuttling miR-130b-3p repressed proliferation, migration, and angiogenesis of HUVECs by regulating ICAM-1 expression.
本研究旨在探讨 miR-130b-3p 和 ICAM-1 在妊娠期糖尿病（GDM）中的作用及其潜在关联。
从 GDM 患者中分离胎盘间充质干细胞（PlaMSCs），检测 GDM 患者来源的 PlaMSCs（GDM-MSCs）及其分泌的外泌体对人脐静脉内皮细胞（HUVEC）增殖、迁移和血管生成的影响。然后，用 miR-130b-3p 反义寡核苷酸转染 GDM-MSCs，修饰 GDM-MSCs 来源的外泌体中的 miR-130b-3p 表达，将修饰后的 miR-130b-3p 表达的外泌体与 HUVEC 共培养，评估外泌体 miR-130b-3p 对 HUVEC 功能的影响。进一步预测和评估 miR-130b-3p 的靶基因。将 miR-130b-3p 修饰的外泌体与转染了 ICAM-1 shRNA 的 HUVEC 共培养，以确定 miR-130b-3p-ICAM-1 相互作用对 HUVEC 功能的影响。此外，还进行了 GDM 小鼠模型实验，以进一步研究 miR-130b-3p 在体内 GDM 中的作用。
GDM-MSCs 抑制 HUVEC 增殖和血管生成。在 GDM-MSCs 来源的外泌体中发现 miR-130b-3p 表达升高。GDM-MSCs 来源的外泌体抑制 HUVEC 的增殖和血管生成，抑制外泌体对 HUVEC 功能的抑制作用。机制上，miR-130b-3p 以靶向方式下调 ICAM-1 的表达，从而增强 HUVEC 的增殖、迁移和血管生成，并增加血管生成相关因子的表达。此外，miR-130b-3p 抑制促进 GDM 小鼠胎盘血管生成，并上调 ICAM-1 表达。
综上所述，GDM-MSCs 来源的外泌体通过调节 ICAM-1 的表达，抑制 HUVEC 的增殖、迁移和血管生成。
