Overexpression of Circ-Astn1 Suppresses Hyperglycemia-Induced Endothelial Cell Damage via the miR-138-5p/SIRT1 Axis  

作　　者：Hong-bin Yu Li-yun Wang Xiao-ning Yan Xue-yan Wu Jian-long Wu Da-wei Liu Si-yang Liu 

机构地区：[1]Chengde Central Hospital,Chengde,067000,China [2]Shanxi Hospital of Integrated Traditional and Western Medicine,The Fourth Clinical College,Shanxi University of Chinese Medicine,Jinzhong,030619,China [3]Department of Human Anatomy,Chengde Medical College,Chengde,067000,China

出　　处：《Current Medical Science》2025年第1期93-103,共11页当代医学科学(英文)

基　　金：supported by grants from the National Natural Science Foundation of China(No.81770483);Shanghai Tenth Hospital’s improvement plan for NSFC(No.04.03.17.070).

摘　　要：Objective To elucidate the regulatory mechanism of circRNAs in diabetic retinopathy.Methods Next-generation sequencing(NGS)was employed to identify circRNAs that are abnormally expressed in endothe-lial progenitor cells(EPCs)under hyperglycemia(HG)conditions.The regulatory mechanism and predicted targets of this circRNA were also studied via bioinformatics analysis,luciferase reporter assays,angiogenic differentiation experiments,flow cytometry,and RT-qPCR.Results Circ-astrotactin 1(circ-Astn1)expression was decreased in EPCs under HG conditions,and circ-Astn1 overexpres-sion inhibited HG-induced endothelial damage.The miR-138-5p and silencing information regulator 2 related enzyme 1(SIRT1)were identified as circ-Astn1 downstream targets,which were further verified through luciferase reporter assays.SIRT1 silencing or miR-138-5p overexpression reversed the protective effect of circ-Astn1 on HG-induced endothelial cell dysfunction,as evidenced by increased apoptosis,abnormal vascular differentiation,and inflammatory factor secretion.SIRT1 overexpression reversed miR-138-5p-induced endothelial cell dysfunction under HG conditions.In vivo experiments confirmed that circ-Astnl overexpression promoted skin wound healing through the regulation of SIRT1.Conclusions These findings suggest that circ-Astn1 promotes SIRT1 expression by sponging miR-138-5p.Circ-Astn1 over-expression suppresses HG-induced endothelial cell damage via miR-138-5p/SIRT1 axis.

关 键 词：Circ-Astn1 Endothelial cell HYPERGLYCEMIA miR-138-5p SIRT1 

分 类 号：R73[医药卫生—肿瘤]