MicroRNA-195-5p facilitates endothelial dysfunction by inhibiting vascular endothelial growth factor A in gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is a common disorder during pregnancy associated with endothelial dysfunction in the placental vasculature. MicroRNAs (miRNAs), which are short noncoding RNAs that modulate post-transcriptional gene expression, affect GDM progression. MiR-195-5p was reported to be a putative biomarker for GDM diagnosis, whose expression was markedly elevated in serum of GDM patients. Therefore, our study intended to explore whether miR-195-5p regulates endothelial cell dysfunction in GDM. Human placental microvascular endothelial cells (hPMECs) were treated with high concentration of glucose to establish an in vitro GDM model. The apoptosis, proliferation and angiogenesis of hPMECs were detected by flow cytometry analysis, CCK-8 assay and tube formation assay. The binding between vascular endothelial growth factor A (VEGFA) and miR-195-5p was verified by luciferase reporter assay. GDM mouse model was established by intraperitoneal injection of streptozocin. Cell apoptosis and the pathological changes in GDM mouse placenta tissues were evaluated by TUNEL staining and HE staining. Gene expression was detected by RT-qPCR. Protein levels were evaluated by western blotting. In this study, miR-195-5p knockdown promoted the proliferation and angiogenesis as well as inhibited the apoptosis of HG-treated hPMECs. MiR-195-5p targeted VEGFA, whose expression was downregulated in HG-treated hPMECs. VEGFA silencing antagonized the influence of miR-195-5p knockdown on the phenotypes of HG-treated hPMECs. Additionally, miR-195-5p inhibition decelerated cell apoptosis and improved pathological changes in GDM mouse placenta tissues. MiR-195-5p level was negatively correlated to VEGFA level in GDM mouse placenta tissues. Overall, miR-195-5p facilitates the endothelial cell dysfunction by inhibiting VEGFA in GDM. (C) 2022 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.

Automated summary

MiR-195-5p is involved in the regulation of endothelial cell dysfunction in gestational diabetes mellitus (GDM) through targeting VEGFA, affecting cell proliferation, apoptosis, and angiogenesis.