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Free Radical Biology and Medicine

Free Radical Biology and Medicine

IF: 7.1
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Transcription factor EGR2 drives cataract formation through IGFBP3-mediated oxidative injury in lens epithelial cells

Published:13 October 2025 DOI: 10.1016/j.freeradbiomed.2025.10.009 PMID: 41093149
Wanqian Li , Yue Zou , Wanqiu Zheng , Jiaojiao Zhang , Chao Cen , Ruonan Li , Hong Cheng , Shengping Hou , Wenjuan Wan , Liang Liang , Juan Kang , Shijie Zheng , Ke Hu

Abstract

Cataracts, a prevalent ocular disorder, represent the leading cause of global blindness. Evidence indicates that oxidative stress-induced lens epithelial cells (LECs) apoptosis constitutes a key pathogenic mechanism in age-related cataract (ARC). Although the transcription factor EGR2 has been recognized as both a novel senescence regulator and a critical mediator in ophthalmic diseases including uveitis and diabetic retinopathy, its precise role in cataract remains undefined. In this study, EGR2 was identified via transcriptome sequencing as a potential core regulator of cataract development. Subsequent investigations demonstrated elevated EGR2 expression in the anterior capsule from cataract patients, oxidatively damaged LECs, and a sodium selenite-induced rat cataract model. Functional studies revealed that EGR2 overexpression exacerbated oxidative stress and promoted apoptosis in LECs. Notably, intravitreal administration of AAV-shEGR2 significantly attenuated lens opacification. RNA-seq and CUT& Tag findings indicated that EGR2 directly bound to its downstream target insulin-like growth factor binding protein 3 (IGFBP3). Furthermore, IGFBP3 silencing effectively reversed EGR2-mediated oxidative injury and apoptosis in LECs, while administration of recombinant IGFBP3 protein accelerated cataract progression in vivo. This study delineates EGR2 as a pivotal regulator in cataract pathogenesis, proposing a novel therapeutic target while uncovering the molecular mechanism of oxidative stress-mediated lens pathology.

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Materials
Procduct Name CAS Molecular Formula Supplier Price
Z-Vad-fmk, non-methylated 161401-82-7 C21H28FN3O7 90 suppliers $70.00-$3200.00
Z-Vad-fmk, non-methylated 161401-82-7 C21H28FN3O7 90 suppliers $70.00-$3200.00
Z-Vad-fmk, non-methylated 161401-82-7 C21H28FN3O7 90 suppliers $70.00-$3200.00
Z-Vad-fmk, non-methylated 161401-82-7 C21H28FN3O7 90 suppliers $70.00-$3200.00

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