MiR-222-3p downregulation prompted the migration, invasion and recruitment of endothelial progenitor cells via ADIPOR1 expression increase-induced AMKP activation

Abstract

BackgroundClinical data show that aneurysm rupture causes high mortality in aged men. MicroRNAs (miRNAs) were reported to regulate endothelial progenitor cells (EPCs) which play a vital role in repairing endothelial damage and maintaining vascular integrity. This study identified a novel miRNA regulator for the functions of EPCs in aneurysm repair. MethodsAbdominal aortic aneurysm (AAA) model was established on Sprague-Dawley rats which later underwent antagomiR-222 treatment. The histopathological changes of AAA rats were examined by hematoxylin-eosin staining. Flow cytometry was performed to quantify EPCs in peripheral blood and identify EPCs isolated from the rat femur. The potential target of miR-222-3p was predicted by TargetScan v7.2 and validated by Dual-luciferase reporter assay. The effects of miR-222-3p and ADIPOR1 on the migration, invasion and tube formation of EPCs were evaluated by wound healing, Transwell and tube formation assays. The expressions of miR-222-3p and ADIPOR1 in aortic aneurysm tissues and EPCs were assessed by qRT-PCR or Western blot. ResultsAAA exhibited histopathological abnormality, a decreased number of EPCs in the peripheral blood and an increased miR-222-3p expression. AntagomiR-222 injection reversed all these phenomena in AAA rats. Upregulating miR-222-3p expression inhibited the migration, invasion, and tube formation of EPCs, and the expressions of ADIPOR1 and phosphorylated-AMKP, while downregulating miR-222-3p expression exerted opposite effects in EPCs. ADIPOR1 was identified as a target gene of miR-222-3p. Overexpressing ADIPOR1 abrogated the effects of miR-222-3p upregulation on EPCs. ConclusionDownregulated miR-222-3p prompted the migration, invasion and recruitment of EPCs by targeting ADIPOR1-induced AMKP activation.