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

Abstract

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 endothelial 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-Astn1 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.

Keywords

Circ-Astn1 / Endothelial cell / Hyperglycemia / miR-138-5p / SIRT1

© The Author(s) 2025

Hong-bin Yu, Li-yun Wang and Xiao-ning Yan contributed equally to this work.

Author Contributions HBY and SYL contributed to the study conception and design. All authors collected the data and performed the data analysis. All authors contributed to the interpretation of the results and the completion of figures. All authors drafted the article and finally approved the submitted version.

Funding This study was supported by grants from the National Natural Science Foundation of China (No. 81770483), and Shanghai Tenth Hospital’s improvement plan for NSFC (No. 04.03.17.070).

Data availability The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Conflict of interest All authors declare that there are no competing interests.

Ethics Approval and Consent to Participate This study was approved by the ethics committee of Institutional Animal Care and Use Committee in Chengde Central Hospital. All procedures performed in the studies involving animals were in accordance with ARRIVE guidelines.

Consent for publication Not applicable.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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