Bone Marrow Mesenchymal Stem Cell-derived Exosomal microRNA-99b-5p Promotes Cell Growth of High Glucose-treated Human Umbilical Vein Endothelial Cells by Modulating THAP Domain Containing 2 Expression

Abstract

Introduction:

Bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) may function as novel candidates for treating diabetic wounds due to their ability to promote angiogenesis.

Materials and Methods:

This study investigated the effects of BMSC-exos on the growth and metastasis of human umbilical vein endothelial cells (HUVECs) treated with high glucose (HG). The exosomes were separated from BMSCs and identified. The cell phenotype was detected by 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and 5-ethynyl-2’-deoxyuridine, wound healing, and transwell assays, while the number of tubes was measured via tube formation assay.

Result:

The RNA and protein expression levels were studied using reverse transcription-quantitative polymerase chain reaction and western blotting, whereas integration of microRNA-99b-5p (miR-99b-5p) with THAP domain containing 2 (THAP2) was confirmed via dual-luciferase reporter and RNA pull-down assays. Results of transmission electron microscopy, nanoparticle tracking analysis, and laser scanning confocal microscopy revealed that exosomes were successfully separated from BMSCs and endocytosed into the cytoplasm by HUVECs. Similarly, BMSC-exos were found to promote the growth of HG-treated HUVECs, while their growth was inhibited by suppressing miR-99b-5p. THAP2 was found to bind to miR-99b-5p, where THAP2 inhibition reversed the miR-99b-5p-induced effects on cell growth, migration, and tube numbers.

Conclusion:

In conclusion, miR-99b-5p in BMSC-exo protects HUVECs by negatively regulating THAP2 expression.