Gene

Endothelial progenitor cell

microRNA

Cell biology

Flow cytometry

Molecular biology

Biology

M2 Macrophage

Microvesicles

Apoptosis

Stem cell

Macrophage polarization

Cancer research

Biochemistry

Environmental health

Downregulation and upregulation

Immunology

Progenitor cell

In vitro

Exosome

Macrophage

Population

Medicine

Chemistry

Cell

Wound healing

Biomedicine & Pharmacotherapy

Diabetes mellitus is a major cause of blindness and chronic ulcers in the working age population worldwide. Former research have found that differentially expressed circular RNAs (circRNAs) are associated with hyperglycemia (HG)-induced endothelial cell damage. And adipose-derived stem cells (ADSCs)-exosome transplant have more therapeutic effect to enhance wound healing in diabetic mice by delivery circRNA. The current investigation employed high-throughput sequencing to identify circRNAs that are abnormally expressed in endothelial progenitor cells (EPCs) under HG conditions. The regulatory mechanism and predicted targets of one differentially expressed circRNA, circ-Snhg11, were investigated utilizing bioinformatics analyses, luciferase reporter assays, angiogenic differentiation assays, flow cytometric apoptosis analysis, and RT-qPCR. The result show that circ-Snhg11 expression decreased in EPCs under HG conditions and that overexpression of circ-Snhg11 suppressed HG-induced endothelial cell damage and M1-like macrophage polarization. miR-144-3p and HIF-1α were identified as downstream targets of circ-Snhg11, which was further verified by luciferase reporter analysis. miR-144-3p overexpression or HIF-1α inhibition reversed circ-Snhg11 protective effect on HG-induced endothelial cell dysfunction, as evidenced by increased apoptosis, abnormal vascular differentiation, and secretion of inflammatory factors. In addition, miR-144-3p overexpression or inhibition of HIF-1α reversed protective effect regarding circ-Snhg11 on M2-like macrophage polarization under HG conditions. These findings suggest that circ-Snhg11 promotes HIF-1α expression through miR-144-3p sponging. Our data demonstrate that circ-Snhg11 overexpression exosome from ADSCs suppresses HG-induced endothelial cell damage and induces M2-like macrophage polarization via the miR-144-3p/HIF-1α axis.

Hypoxic ADSC-derived exosomes enhance wound healing in diabetic mice via delivery of circ-Snhg11 and induction of M2-like macrophage polarization