M2巨噬细胞
巨噬细胞极化
伤口愈合
祖细胞
外体
内皮祖细胞
小RNA
癌症研究
细胞凋亡
人口
细胞生物学
流式细胞术
微泡
下调和上调
化学
细胞
生物
干细胞
巨噬细胞
分子生物学
免疫学
医学
基因
生物化学
体外
环境卫生
作者
Rongfeng Shi,Yinpeng Jin,Song Zhao,Haiyan Yuan,Jiahai Shi,Hui Zhao
标识
DOI:10.1016/j.biopha.2022.113463
摘要
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.
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