2. Academic Validation
  3. CircTHADA regulates endothelial cell pyroptosis in diabetic retinopathy through miR-494-3p/CASP1/GSDMD-N/IL-1β pathway

CircTHADA regulates endothelial cell pyroptosis in diabetic retinopathy through miR-494-3p/CASP1/GSDMD-N/IL-1β pathway

  • Exp Cell Res. 2025 Apr 15;447(2):114496. doi: 10.1016/j.yexcr.2025.114496.
Shuai He 1,  Chufeng Gu 2,  Chunren Meng 3,  Chunyang Cai 4,  Dongwei Lai 4,  Qinghua Qiu 5
Affiliations

Affiliations

  • 1 School of Life Sciences, Westlake University, Westlake Laboratory of Life Sciences and Biomedicine, Institute of Basic Medical Science, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, PR China.
  • 2 Department of Ophthalmology, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, PR China; Shengli Clinical College of Fujian Medical University, Fuzhou, Fujian, PR China. Electronic address: guchufeng@fjsl.com.cn.
  • 3 Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, PR China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, PR China.
  • 4 Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, PR China.
  • 5 Department of Ophthalmology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. Electronic address: qinghuaqiu@163.com.
PMID: 40090540 DOI: 10.1016/j.yexcr.2025.114496
Abstract

Our study aimed to elucidate the mechanism by which circTHADA competitively adsorbs miR-494-3p to regulate CASP1-mediated endothelial cell (EC) Pyroptosis in diabetic retinopathy (DR). To be specific, we used high glucose (HG)-induced human retinal microvascular endothelial cells (HRMECs) as DR cell models and streptozotocin (STZ)-treated mice as DR mouse models. The expression levels of circTHADA, miR-494-3p, CASP1, NLRP3, GSDMD-N and IL-1β were detected and flow cytrometry was applied to measure cell Pyroptosis rate and dual luciferase reporter assays were utilized to determine the direct binding sites. As a result, exacerbated EC Pyroptosis in DR was detected in DR cell and mouse models. Based on differentially expressed circRNA profiles by microarray and experimental verification, circTHADA was filtered and identified to regulate CASP1-mediated EC Pyroptosis. miR-494-3p was then proven to be involved in circTHADA-mediated ceRNA network by bioinformatics analysis and experimental verification. Further gain- and loss-of-function experiments and rescue experiments revealed the function of the circTHADA/miR-494-3p/CASP1 axis in Pyroptosis.

Keywords

CASP1; DR; ECs pyroptosis; ceRNA network; circTHADA.

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