Zeb1通过维持上皮再生促进氮芥诱导的角膜上皮伤口愈合。

IF 4.7 2区医学 Q1 OPHTHALMOLOGY

Investigative ophthalmology & visual science Pub Date : 2025-09-02 DOI:10.1167/iovs.66.12.33

Fuhua Wang, Xiaolei Sun, Yanling Dong, Fang Cheng, Jiangli Fan, Xiaoqin Lu, Douglas Emery, Hui Shao, Wei Wang, Lijun Zhang, Douglas C Dean, Yongqing Liu

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引用次数: 0

摘要

目的：探讨Zeb1对氮芥（NM）诱导的小鼠急性角膜上皮损伤及其恢复的调控作用。方法：本研究采用局部荧光素染色和切片免疫组化对Zeb1野生型和杂合子敲除小鼠进行纳米诱导的急性角膜上皮损伤及恢复进行评价，并采用实时定量PCR和染色质免疫沉淀法研究Zeb1调控急性角膜上皮损伤及恢复的机制。结果：在角膜中央局部应用NM可立即降低Zeb1表达，随后发生去上皮和上皮细胞死亡，同时细胞增殖导致上皮细胞恢复。单等位基因敲除Zeb1可降低纳米颗粒诱导的急性上皮损伤，但可延缓损伤的恢复。结论：Zeb1通过维持上皮的可再生性促进纳米颗粒诱导的角膜上皮创面愈合，是减少急性芥子气角膜病变早期眼部发病的潜在治疗靶点。

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Zeb1 Facilitates Nitrogen Mustard-Induced Corneal Epithelial Wound Healing by Maintaining Epithelial Renewability.

Purpose: To characterize Zeb1 regulation of nitrogen mustard (NM)-induced acute corneal epithelial damage and its recovery in mice.

Methods: This study utilized topical fluorescein staining and section immunohistochemistry to evaluate NM-induced acute corneal epithelial damage and its recovery in both Zeb1 wild-type and heterozygous knockout mice, as well as real-time quantitative PCR and chromatin immunoprecipitation to delineate the mechanism underlying Zeb1 regulation of such corneal epithelial damage and recovery.

Results: Topical application of NM on the central cornea causes an immediate reduction of Zeb1 expression, followed by de-epithelization and epithelial cell death, along with cell proliferation resulting in epithelial recovery. Monoallelic knockout of Zeb1 decreased NM-induced acute epithelial damage but delayed the recovery from the damage.

Conclusions: Zeb1 facilitates NM-induced corneal epithelial wound healing by maintaining epithelial renewability and thus is a potential therapeutic target to reduce acute mustard gas keratopathy in early ocular pathogenesis.

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来源期刊

Investigative ophthalmology & visual science 医学-眼科学

CiteScore

6.90

自引率

4.50%

发文量

339

审稿时长

1 months

期刊介绍： Investigative Ophthalmology & Visual Science (IOVS), published as ready online, is a peer-reviewed academic journal of the Association for Research in Vision and Ophthalmology (ARVO). IOVS features original research, mostly pertaining to clinical and laboratory ophthalmology and vision research in general.