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

Won-Yong Jeong; Hye-Young Yoo; Chan-Wha Kim

doi:10.1016/j.bbrc.2018.01.054

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

Biochem Biophys Res Commun. 2018 Feb 5;496(2):359-366. doi: 10.1016/j.bbrc.2018.01.054. Epub 2018 Jan 10.

Authors

Won-Yong Jeong¹, Hye-Young Yoo¹, Chan-Wha Kim²

Affiliations

¹ Department of Biotechnology, BK21 Plus Program, College of Life Sciences and Biotechnology, Korea University, 1-5, Anam Dong, Seongbuk-Gu, Seoul 136-701, South Korea.
² Department of Biotechnology, BK21 Plus Program, College of Life Sciences and Biotechnology, Korea University, 1-5, Anam Dong, Seongbuk-Gu, Seoul 136-701, South Korea. Electronic address: cwkim@korea.ac.kr.

PMID: 29331377
DOI: 10.1016/j.bbrc.2018.01.054

Abstract

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.

Keywords: Cell migration; Corneal cell; Proliferation; Wound healing; β-cellulin.

MeSH terms

ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics
ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism
Animals
Betacellulin / pharmacology*
Cell Movement / drug effects
Cell Proliferation / drug effects
Epithelial Cells / drug effects*
Epithelial Cells / metabolism
Epithelial Cells / pathology
Epithelium, Corneal / drug effects*
Epithelium, Corneal / injuries
Epithelium, Corneal / metabolism
Gene Expression Regulation
Mice
Mice, Inbred BALB C
Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
Mitogen-Activated Protein Kinase 1 / genetics*
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
Mitogen-Activated Protein Kinase 3 / genetics*
Mitogen-Activated Protein Kinase 3 / metabolism
Organ Culture Techniques
Phosphoproteins / genetics
Phosphoproteins / metabolism
Phosphorylation / drug effects
Polycomb Repressive Complex 1 / genetics
Polycomb Repressive Complex 1 / metabolism
Protein Kinase Inhibitors / pharmacology
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism
Stem Cells / drug effects*
Stem Cells / metabolism
Stem Cells / pathology
Trans-Activators / genetics
Trans-Activators / metabolism
Wound Healing / drug effects
Wound Healing / genetics

Substances

ATP Binding Cassette Transporter, Subfamily G, Member 2
Abcg2 protein, mouse
Betacellulin
Bmi1 protein, mouse
Btc protein, mouse
Phosphoproteins
Protein Kinase Inhibitors
Proto-Oncogene Proteins
Trans-Activators
Trp63 protein, mouse
Polycomb Repressive Complex 1
Mapk1 protein, mouse
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3