Work

ELAVL1 Stabilizes HMOX1 mRNA to Drive Ferroptosis in Diabetic Retinopathy

Year: 2025

Type: article

Abstract: Objective: This study aims to investigate the role of heme oxygenase 1 (HMOX1) in the pathogenesis of diabetic retinopathy (DR) and identify the RNA-binding protein embryonic lethal abnormal vision-like 1 (ELAVL1) as a novel regulator of HMOX1 mRNA stability driving ferroptosis, proposing ELAVL1 as a potential therapeutic target for DR. Methods: DR was modeled in vitro using high glucose (HG)-treated ARPE19 cells and in vivo via streptozotocin (STZ)-induced diabetic rats. Cell damage was assessed through measuring cell viability, oxidative stress markers, iron content, and ferroptosis-related protein expression. HMOX1 expression and its regulatory interaction with ELAVL1 were analyzed using RT-qPCR, immunohistochemistry, Western blotting, RNA-fluorescence in situ hybridization, and RNA immunoprecipitation. Functional roles were validated by gene knockdown or overexpression experiments. Results: HG stimulation induced ferroptosis-related damage and oxidative stress in ARPE19 cells and the retinas of DR rats, accompanied by a significant upregulation of HMOX1 expression (approximately 165% in vivo and 189% in vitro). Knockdown of either HMOX1 or ELAVL1 effectively suppressed ferroptosis and mitigated retinal degeneration. Conclusion: HMOX1 is critical for ferroptosis-mediated retinal damage in DR, and ELAVL1 promotes ferroptosis predominantly by stabilizing HMOX1 mRNA.

Source: Diabetes Metabolic Syndrome and Obesity

DOI: 10.2147/dmso.s536325

Authors: Yanjun Gao, Wenjing Zhao, Qiannan Chai, Cunxi Ye

Institutions: Hebei Medical University, Second Hospital of Hebei Medical University

Language: English

Topic: Retinal Diseases and Treatments

Subfield: Ophthalmology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,836