MicroRNA-126 enhances the biological function of endothelial progenitor cells under oxidative stress via PI3K/Akt/GSK3β and ERK1/2 signaling pathways

Qinqin Wu; Benling Qi; Xiaoyu Duan; Xiaoyan Ming; Fengqin Yan; Yingxia He; Xiaofen Bu; Shan Sun; Hong Zhu

doi:10.17305/bjbms.2019.4493

Authors

Qinqin Wu Department of Gerontology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Benling Qi Department of Geriatrics, Institute of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Xiaoyu Duan Department of Gerontology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Xiaoyan Ming Department of Gerontology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China https://orcid.org/0000-0001-8017-6898
Fengqin Yan Department of Gerontology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Yingxia He Department of Gerontology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Xiaofen Bu Department of Gerontology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Shan Sun Department of Gerontology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Hong Zhu Department of Gerontology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

DOI:

https://doi.org/10.17305/bjbms.2019.4493

Keywords:

Acute myocardial infarction, AMI, endothelial progenitor cells, EPC, PI3K/Akt/GSK3β pathway, ERK1/2

Abstract

Endothelial progenitor cell (EPC) transplantation is a safe and effective method to treat acute myocardial infarction (AMI). However, oxidative stress leads to the death of a large number of EPCs in the early stage of transplantation, severely weakening the therapeutic effect. Previous studies demonstrated that microRNAs regulate the biological function of EPCs. The aim of the current study was to investigate the effect of microRNA on the biological function of EPCs under oxidative stress. Quantitative reverse transcription PCR was performed to detect the expression of miR-126, miR-508-5p, miR-150, and miR-16 in EPCs from rats, among which miR-126 showed a relatively higher expression. Treatment with H₂O₂ decreased miR-126 expression in EPCs in a dose-dependent manner. EPCs were further transfected with miR-126 mimics or inhibitors, followed by H₂O₂treatment. Overexpression of miR-126 enhanced the proliferation, migration, and tube formation of H₂O₂-treated EPCs. MiR-126 overexpression also inhibited reactive oxygen species and malondialdehyde levels and enhanced superoxide dismutase levels, as well as increased angiopoietin (Ang)1 expression and decreased Ang2 expression in H₂O₂-treated EPCs. Moreover, miR-126 participated in the regulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase 3β (GSK3β) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in EPCs, where both pathways were activated after miR-126 overexpression in H₂O₂-treated EPCs. Overall, we showed that miR-126 promoted the biological function of EPCs under H₂O₂-induced oxidative stress by activating the PI3K/Akt/GSK3β and ERK1/2 signaling pathway, which may serve as a new therapeutic approach to treat AMI.