Human placenta mesenchymal stem cell-derived exosome shuttling microRNA-130b-3p from gestational diabetes mellitus patients targets ICAM-1 and perturbs human umbilical vein endothelial cell angiogenesis,Acta Diabetologica

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Human placenta mesenchymal stem cell-derived exosome shuttling microRNA-130b-3p from gestational diabetes mellitus patients targets ICAM-1 and perturbs human umbilical vein endothelial cell angiogenesis
Acta Diabetologica ( IF 3.1 ) Pub Date : 2022-06-08 , DOI: 10.1007/s00592-022-01910-2
Zhou Gao ₁ , Nan Wang ₁ , Xinli Liu ₁

Affiliation

Objective

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.

Methods

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.

Results

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.

Conclusion

Conclusively, GDM-MSCs-derived exosomes shuttling miR-130b-3p repressed proliferation, migration, and angiogenesis of HUVECs by regulating ICAM-1 expression.

中文翻译：

来自妊娠期糖尿病患者的人胎盘间充质干细胞衍生的外泌体穿梭 microRNA-130b-3p 靶向 ICAM-1 并扰乱人脐静脉内皮细胞血管生成

客观的

本研究的目的是调查 miR-130b-3p 和 ICAM-1 在妊娠期糖尿病 (GDM) 中的作用及其潜在关联。

方法

从GDM患者中分离人胎盘间充质干细胞（PlaMSCs），研究GDM患者的PlaMSCs（GDM-MSCs）和GDM-MSCs分泌的外泌体对人脐静脉内皮细胞（HUVEC）增殖、迁移和迁移的影响检测到血管生成。接下来，用 miR-130b-3p antagomir 转染 GDM-MSCs 以修饰 GDM-MSCs 衍生的外泌体中 miR-130b-3p 的表达，并将具有修饰的 miR-130b-3p 表达的外泌体与 HUVECs 一起培养以评估外泌体 miR- 130b-3p 关于 HUVEC 功能。此外，预测和评估了 miR-130b-3p 的靶基因。将 miR-130b-3p 修饰的外泌体与转染 ICAM-1 shRNA 的 HUVEC 一起培养，以确定 miR-130b-3p-ICAM-1 串扰对 HUVEC 功能的影响。此外，

结果

GDM-MSCs 抑制 HUVEC 增殖和血管生成。在 GDM-MSCs 衍生的外泌体中发现 miR-130b-3p 的表达升高。GDM-MSCs衍生的外泌体抑制HUVECs的增殖和血管生成，抑制miR-130b-3p可以抑制外泌体对HUVEC功能的抑制。从机制上讲，miR-130b-3p 以靶向方式下调 ICAM-1 表达，从而增强 HUVEC 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，抑制 miR-130b-3p 可促进 GDM 小鼠胎盘血管生成并上调 ICAM-1 表达。