Zeb1 facilitates corneal epithelial wound healing by maintaining corneal epithelial cell viability and mobility.
Zeb1 facilitates corneal epithelial wound healing by maintaining corneal epithelial cell viability and mobility.
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DOI：
10.1038/s42003-023-04831-0
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发表时间：
2023-04-20
影响因子：
5.9
通讯作者：
Liu, Yongqing
中科院分区：
文献类型：
--
作者：
Zhang, Yingnan;Do, Khoi K.;Wang, Fuhua;Lu, Xiaoqin;Liu, John Y.;Li, Chi;Ceresa, Brian P.;Zhang, Lijun;Dean, Douglas C.;Liu, Yongqing
角膜是最外层的眼部组织，在保护眼睛免受环境损害方面起着重要作用。角膜上皮损伤引起疼痛和恐惧，并导致全球大多数眼外伤急诊评估。ZEB 1是发育过程中的一个重要转录因子，但其在成体组织中的作用尚不清楚。我们确定Zeb 1是促进角膜上皮伤口愈合的内在因子。在这项研究中，我们证明，Zeb 1的单等位基因缺失显着加速角膜细胞死亡，抑制角膜上皮EMT相关的细胞迁移后，上皮清创。我们提供的证据表明，Zeb 1调节角膜上皮伤口愈合是通过抑制TNF α诱导的上皮细胞死亡所需的基因和诱导有益于上皮细胞迁移的基因。我们认为使用TNF-α拮抗剂可以减少TNF/TNFR 1诱导的角膜上皮细胞死亡和角膜基质炎症，从而帮助角膜伤口愈合。Zeb 1通过抑制TNFα诱导的上皮细胞死亡基因和上调上皮细胞向间质转化和细胞外基质相关基因促进角膜上皮伤口愈合。
The cornea is the outmost ocular tissue and plays an important role in protecting the eye from environmental insults. Corneal epithelial wounding provokes pain and fear and contributes to the most ocular trauma emergency assessments worldwide. ZEB1 is an essential transcription factor in development; but its roles in adult tissues are not clear. We identify Zeb1 is an intrinsic factor that facilitates corneal epithelial wound healing. In this study, we demonstrate that monoallelic deletion of Zeb1 significantly expedites corneal cell death and inhibits corneal epithelial EMT-related cell migration upon an epithelial debridement. We provide evidence that Zeb1-regulation of corneal epithelial wound healing is through the repression of genes required for Tnfa-induced epithelial cell death and the induction of genes beneficial for epithelial cell migration. We suggest utilizing TNF-α antagonists would reduce TNF/TNFR1-induced cell death in the corneal epithelium and inflammation in the corneal stroma to help corneal wound healing. Zeb1 facilitates corneal epithelial wound healing by repressing TNFα-induced epithelial cell death genes and upregulating epithelial to mesenchymal transition and extracellular matrix-related genes.
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影响因子：
6.6
作者：
Katsura A;Tamura Y;Hokari S;Harada M;Morikawa M;Sakurai T;Takahashi K;Mizutani A;Nishida J;Yokoyama Y;Morishita Y;Murakami T;Ehata S;Miyazono K;Koinuma D
通讯作者：
Koinuma D
影响因子：
17.8
作者：
Ljubimov AV;Saghizadeh M
通讯作者：
Saghizadeh M
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影响因子：
5.6
作者：
Lousa I;Reis F;Santos-Silva A;Belo L
通讯作者：
Belo L
影响因子：
4.8
作者：
Drake, Justin M.;Barnes, J. Matthew;Henry, Michael D.
通讯作者：
Henry, Michael D.
影响因子：
23.9
作者：
Liu Y;Clem B;Zuba-Surma EK;El-Naggar S;Telang S;Jenson AB;Wang Y;Shao H;Ratajczak MZ;Chesney J;Dean DC
通讯作者：
Dean DC