Zeb1 facilitates corneal epithelial wound healing by maintaining corneal epithelial cell viability and mobility

Yingnan Zhang; Khoi K Do; Fuhua Wang; Xiaoqin Lu; John Y Liu; Chi Li; Brian P Ceresa; Lijun Zhang; Douglas C Dean; Yongqing Liu

doi:10.1038/s42003-023-04831-0

Zeb1 facilitates corneal epithelial wound healing by maintaining corneal epithelial cell viability and mobility

Commun Biol. 2023 Apr 20;6(1):434. doi: 10.1038/s42003-023-04831-0.

Authors

Yingnan Zhang^#^{1

2}, Khoi K Do^#¹, Fuhua Wang^{1

3}, Xiaoqin Lu^{1

4}, John Y Liu¹, Chi Li^{1

4}, Brian P Ceresa⁵, Lijun Zhang⁶, Douglas C Dean^{7

8

9}, Yongqing Liu^{10

11

12}

Affiliations

¹ Department of Medicine, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
² The Rosenberg School of Optometry, University of the Incarnate Word, San Antonio, TX, 78229, USA.
³ Eye Institute and Eye Hospital of Shangdong First Medical University, 250021, Jinan, China.
⁴ James Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
⁵ Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
⁶ Department of Ophthalmology, Third People's Hospital of Dalian, Dalian Medical University, 116033, Dalian, China.
⁷ Department of Medicine, University of Louisville School of Medicine, Louisville, KY, 40202, USA. douglas.dean@louisville.edu.
⁸ James Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, 40202, USA. douglas.dean@louisville.edu.
⁹ Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, KY, 40202, USA. douglas.dean@louisville.edu.
¹⁰ Department of Medicine, University of Louisville School of Medicine, Louisville, KY, 40202, USA. y0liu016@louisville.edu.
¹¹ James Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, 40202, USA. y0liu016@louisville.edu.
¹² Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, KY, 40202, USA. y0liu016@louisville.edu.

^# Contributed equally.

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cornea / metabolism
Corneal Injuries* / genetics
Corneal Injuries* / metabolism
Epithelial Cells
Epithelium, Corneal* / metabolism
Humans
Wound Healing / genetics
Zinc Finger E-box-Binding Homeobox 1 / genetics
Zinc Finger E-box-Binding Homeobox 1 / metabolism

Substances

ZEB1 protein, human
Zinc Finger E-box-Binding Homeobox 1

Abstract

Publication types

MeSH terms

Substances

Grants and funding