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Brian P. Ceresa, Joanne Peterson, Eric D. Phelps; Betacellulin-Mediated Corneal Epithelial Cell Migration. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1825.
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© ARVO (1962-2015); The Authors (2016-present)
The epidermal growth factor receptor (EGFR) is a cell surface receptor tyrosine kinase that plays a critical role in the homeostasis and healing of the corneal epithelium. Stimulation with epidermal growth factor (EGF) has limited therapeutic utility. Another endogenous EGFR ligand, betacellulin (BTC), is a more efficacious activator of corneal epithelial wound healing. In this study, we explore the molecular basis for BTC’s enhanced efficacy as compared to EGF.
The molecular basis for the differences between BTC and EGF was studied with telomerase immortalized human corneal epithelial (hTCEpi) and primary corneal epithelial (HCEC) cells. The dose dependent BTC- and EGF-mediated cell migration was monitored. Semi-quantitative polymerase chain reaction (PCR) and immunoblots were used to determine which EGFR family members were present. Radioligands were used to measure the pH dependence of binding.
BTC is a more efficacious activator of corneal epithelial cell migration than EGF. EGFR and its family members ErbB2 and ErbB3 were present in immortalized and primary corneal epithelial cells. ErbB4 was not. Binding of EGF to EGFR was more sensitive to changes in pH than BTC binding to EGFR.
BTC is a more efficacious activator of corneal epithelial cell migration than EGF. BTC can bind to and activate the ErbB4, but does not in corneal epithelial cells, as it is not present in either primary or immortalized corneal cells. Differences in ligand:receptor binding, not selectivity in ErbB family member, is the likely molecular basis for BTC’s enhanced signaling.
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