β-cellulin promotes the proliferation of corneal epithelial stem cells through the phosphorylation of erk1/2

The proliferation of corneal epithelial stem cells (CESCs) is a very important process in the recovery of corneal wounds. Recent studies have shown that β-cellulin (BC) is effective in the repair of other tissues. However, its mechanism of action in corneal wound healing is not yet clear. The purpose of this study was to investigate how BC accelerates wound healing of the cornea. Here, we confirmed that the proliferation of CESCs was induced at a specific concentration (0.2, 2 and 20 ng/mL) by treatment with BC. Markers associated with proliferation activity (ΔNp63, bmi-1, abcg2) were also upregulated. In vivo experiments showed that the corneal wound healing rate was increased in mice. We found that BC stimulates the phosphorylation of the erk1/2 signaling pathway, which is triggered during the recovery of mouse corneal wounds. However, the inhibition of erk1/2 phosphorylation delayed the recovery of mouse corneal wounds in an organ culture assay. According to these results, BC may be a potential treatment factor for corneal wound healing.