Egr‑1 promotes the proliferation and migration of vascular smooth muscle cells by transcriptionally activating Egr‑2 in arteriovenous fistulas

Hu,Ke; Bu,Shichen; Guo,Yi; Li,Yuxuan; Yu,Shiwen; Wang,Lulu; Cai,Chuanqi; Li,Yiqing; Liu,Xin; Huang,Hegui; Wang,Weici

doi:10.3892/ijmm.2025.5568

Egr‑1 promotes the proliferation and migration of vascular smooth muscle cells by transcriptionally activating Egr‑2 in arteriovenous fistulas

Authors:
- Ke Hu
- Shichen Bu
- Yi Guo
- Yuxuan Li
- Shiwen Yu
- Lulu Wang
- Chuanqi Cai
- Yiqing Li
- Xin Liu
- Hegui Huang
- Weici Wang
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Affiliations: Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Cardiology, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361006, P.R. China, Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430022, P.R. China, Department of Pharmacy, Wuhan No. 1 Hospital, Wuhan, Hubei 430022, P.R. China
Published online on: June 23, 2025 https://doi.org/10.3892/ijmm.2025.5568
Article Number: 127

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Abstract

Arteriovenous fistulas (AVFs) are preferred access points for hemodialysis. The present study aimed to investigate the function of early growth response‑1 (Egr‑1) in the proliferation and migration of smooth muscle cells (SMCs) and assess its potential as a new therapeutic target for AVF treatment. A comprehensive analysis combining public data‑source mining, human tissue collection, animal studies, cell culture experiments and various molecular biology techniques was conducted. The public dataset GSE119296 was used for immunohistochemical analyses of human AVF stenosis samples. SMC‑specific Egr‑1 knockout mice and various in vitro assays on primary rat vascular SMCs were used to evaluate the effect of Egr‑1 on the functional capacity of SMCs. RNA sequencing and chromatin immunoprecipitation sequencing was performed. Egr‑1 was upregulated in human AVF stenosis samples and cultured SMCs. Knockout of Egr‑1 in mice mitigated AVF outflow tract stenosis, improved flow dynamics and diminished neointima formation. In vitro, Egr‑1 ablation reduced SMC proliferation and migration; Egr‑1 transcriptionally activated Egr‑2. Increased Egr‑1 expression facilitated SMC proliferation and migration through Egr‑2 regulation, contributing to AVF stenosis. Consequently, targeting Egr‑1 may offer a novel therapeutic approach for managing AVF intimal hyperplasia and improving AVF patency and function in patients with end‑stage renal disease.

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