WNT16B enhances the proliferation and self-renewal of limbal epithelial cells via CXCR4/MEK/ERK signaling

Songjiao Zhao; Xichen Wan; Yiqin Dai; Lan Gong; Qihua Le

doi:10.1016/j.stemcr.2022.03.001

WNT16B enhances the proliferation and self-renewal of limbal epithelial cells via CXCR4/MEK/ERK signaling

Stem Cell Reports. 2022 Apr 12;17(4):864-878. doi: 10.1016/j.stemcr.2022.03.001. Epub 2022 Mar 31.

Authors

Songjiao Zhao¹, Xichen Wan¹, Yiqin Dai², Lan Gong³, Qihua Le⁴

Affiliations

¹ Department of Ophthalmology, Eye, Ear, Nose & Throat Hospital of Fudan University, No. 83 Fenyang Road, Shanghai 200031, China.
² Department of Ophthalmology, Eye, Ear, Nose & Throat Hospital of Fudan University, No. 83 Fenyang Road, Shanghai 200031, China; Research Center, Eye, Ear, Nose & Throat Hospital of Fudan University, Shanghai 200031, China; Myopia Key Laboratory of Ministry of Health, Eye, Ear, Nose & Throat Hospital of Fudan University, Shanghai 200031, China.
³ Department of Ophthalmology, Eye, Ear, Nose & Throat Hospital of Fudan University, No. 83 Fenyang Road, Shanghai 200031, China; Myopia Key Laboratory of Ministry of Health, Eye, Ear, Nose & Throat Hospital of Fudan University, Shanghai 200031, China. Electronic address: 13501798683@139.com.
⁴ Department of Ophthalmology, Eye, Ear, Nose & Throat Hospital of Fudan University, No. 83 Fenyang Road, Shanghai 200031, China; Research Center, Eye, Ear, Nose & Throat Hospital of Fudan University, Shanghai 200031, China; Myopia Key Laboratory of Ministry of Health, Eye, Ear, Nose & Throat Hospital of Fudan University, Shanghai 200031, China. Electronic address: qihuale_eent@163.com.

Abstract

Culture of limbal epithelial cells (LECs) provides the principal source of transplanted limbal stem cells (LESCs) for treatment of limbal-stem-cell deficiency. Optimization of the culture conditions for in-vitro-expanded LECs will help to create a graft with an optimized quality and quantity of LESCs. This study aimed to investigate the effects of WNT16B on LECs and corneal wound healing and the underlying mechanism. Treatment with exogenous WNT16B increased the proliferative capacity and self-renewal of LECs in the cultures. We further revealed that C-X-C chemokine receptor type 4 (CXCR4) was vital for the effects of WNT16B, and activation of CXCR4/MEK/ERK signaling was pivotal in mediating the effects of WNT16B on LECs enriched for LESCs. The stimulatory effect of WNT16B on corneal epithelial repair was confirmed in a mouse corneal-wound-healing model. In summary, WNT16B enhances proliferation and self-renewal of LECs via the CXCR4/MEK/ERK signaling cascade and accelerates corneal-epithelial wound healing.

Keywords: CXCR4; WNT16B; limbal epithelial stem cell; proliferation; self-renewal.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Proliferation / physiology
Cells, Cultured
Epithelial Cells / metabolism
Epithelium, Corneal* / metabolism
Limbus Corneae* / metabolism
Mice
Mitogen-Activated Protein Kinase Kinases / metabolism
Receptors, CXCR4* / metabolism
Wnt Proteins* / metabolism
Wound Healing / physiology

Substances

CXCR4 protein, mouse
Receptors, CXCR4
Wnt Proteins
Mitogen-Activated Protein Kinase Kinases