Zeb1 regulation of wound-healing-induced inflammation in alkali-damaged corneas

Wei Liang; Yingnan Zhang; Liang Zhou; Xiaoqin Lu; Margaret E Finn; Wei Wang; Hui Shao; Douglas C Dean; Lijun Zhang; Yongqing Liu

doi:10.1016/j.isci.2022.104038

Zeb1 regulation of wound-healing-induced inflammation in alkali-damaged corneas

iScience. 2022 Mar 8;25(4):104038. doi: 10.1016/j.isci.2022.104038. eCollection 2022 Apr 15.

Authors

Wei Liang^{1

2}, Yingnan Zhang^{1

3}, Liang Zhou^{4

5}, Xiaoqin Lu^{1

3}, Margaret E Finn^{1

3}, Wei Wang⁴, Hui Shao⁴, Douglas C Dean^{1

3

4}, Lijun Zhang², Yongqing Liu^{1

3

4}

Affiliations

¹ Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.
² Department of Ophthalmology, Third People's Hospital of Dalian, Dalian Medical University, Dalian 116033, China.
³ James Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA.
⁴ Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, KY 40202, USA.
⁵ Department of Ophthalmology, Second Xiangya Hospital of Central South University, Changsha, China.

Abstract

The cornea is an avascular tissue for vision clarity. Alkali burn could cause severe traumatic damage on the cornea with inflammation and neovascularization (NV), leading to vision reduction and blindness. Mechanisms underlying corneal inflammation and NV are not as clear. We previously reported that Zeb1 is an important factor in corneal NV, and we sought to clarify whether it is also involved in regulation of corneal inflammation. We analyzed the alkali burn-induced corneal inflammation and wound healing in both Zeb1^+/+ and Zeb1^-/+ littermates through a multidisciplinary approach. We provide evidence that Zeb1 forms a positive regulatory loop with Tgfb to regulate early corneal inflammation by maintenance of immune cell viability and mobility and later wound healing by activation of both Nf-κb and Tgfb-related Stat3 signaling pathways. We believe that ZEB1 is a potential therapeutic target, and inactivation of ZEB1 could be a strategy to treat severe corneal inflammation condition.

Keywords: Biological sciences; Immunology; Ophthalmology.

Grants and funding

T35 EY026509/EY/NEI NIH HHS/United States