Suppression of PNPase Alleviates Gestational Diabetes Mellitus-cardiovascular Injury through Up-regulating MicroRNA-26a and Down-regulating PTEN

Abstract

\n Objective: Gestational diabetes mellitus (GDM) is often accompanied by cardiovascular injury (CI), while the specific pathology remains largely unknown. The purpose of this study was to investigate the role of Polynucleotide Phosphorylase (PNPase) in GDM-CI.Methods: GDM-CI rats were modeled by giving high-glucose and high-saturated fat compound feed, and PNPase and miR-26a expression in rats was determined. Vascular smooth muscle cells (VSMCs) were isolated, and cells were transfected with si-PNPase, miR-26a mimic, or si-PNPase + miR-26a inhibitor. Cell proliferation, apoptosis and migration of VSMCs were measured by CCK-8 assay, flow cytometry, and scratch test. Dual-luciferase reporter gene assay was performed to verify the targeting relationship between miR-26a and PTEN. RT-qPCR was implemented to detect the expression levels of miR-26a and PTEN among cells in each group.Results: GDM-CI increased PNPase expression and decreased miR-26a expression in cardiovascular tissues of GDM-CI rats. Silencing PNPase and miR-26a upregulation reduced VSMC apoptosis, and enhanced proliferation and migration abilities in GDM-CI. Treatment with miR-26a inhibitor reversed the alleviating effect of inhibiting PNPase expression on GDM-CI. There was a targeting relationship between miR-26a and PTEN, and miR-26a mimic inhibited the expression of PTEN. Suppressed PTEN was found to relieve the GDM-CI.Conclusion: This study suggests that suppression of PNPase alleviates GDM-CI through up-regulating miR-26a and down-regulating PTEN.