[Effects of human placental mesenchymal stem cell (hPDMSC)-derived exosome (PdE) shuttling miR-144-3p on vascular endothelial cell dysfunction in gestational diabetes mellitus (GDM)].

Objective Gestational diabetes mellitus (GDM) is associated with long-term endothelial dysfunction of maternal-fetal vessels, and human placental mesenchymal stem cell (hPDMSC)-derived exosomes (PdE) from GDM patients are closely related to the progression of the disease. This study aims to investigate the expression of miR-144-3p in PdE and its effects and the underlying mechanism on vascular endothelial cell dysfunction in GDM. Methods PdE from normal pregnant patients and GDM patients (the Nor-PdE group and the GDM-PdE group) were isolated and collected. Anti-miR144-3p and negative control were transfected into hPDMSC using the Lipofectamine. Then, the PdE were collected and co-cultured with human umbilical vein endothelial cell (HUVEC). Real-time quantitative PCR (qRT-PCR) was performed to detect miR-144-3p expression, while the CCK-8 assay was used to assess HUVEC viability. TranswellTM assay was performed to analyze cell migration. Matrix gel tube formation assay was carried out to determine tube formation ability. Bioinformatics and dual-luciferase reporter analysis were used to evaluate the targeting relationship between miR-144-3p and suppressors of cytokine signaling 6 (SOCS6). The protein expression of SOCS6 was analyzed by Western blot. Results The PdE from normal pregnant patients and GDM patients were successfully isolated. Compared with Nor-PdE group, the expression levels of miR-144-3p were increased in GDM-PdE group. Moreover, the expression of miR-144-3p was obviously decreased after anti-miR-144-3p treatment. Compared with Nor-PdE group, GDM-PdE treatment dramatically suppressed HUVEC viability, migration and tube formation, these inhibitory effects were markedly attenuated upon miR-144-3p knockdown. Compared with Nor-PdE group, the transcriptional levels of SOCS6 were decreased in HUVECs after treatment with GDM-PdE. Bioinformatics and dual-luciferase reporter analysis confirmed that SOCS6 was a potential target of miR-144-3p. Down-regulation of miR-144-3p obviously increased HUVEC viability, migration and tube formation under GDM-PdE condition, which was abrogated after SOCS6 down-regulation. Conclusion Abnormal high expression of miR-144-3p in GDM-PdE may regulate the dysfunction of vascular endothelial cells by targeting SOCS6, supporting it as a new potential target for PdE in the prevention and treatment of GDM.