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

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.