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B. P. Ceresa, J. L. McClintock; TGF-Alpha Enhances Corneal Epithelial Cell Migration Through Slowed Degradation of the Activated EGFR. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2589.
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The goal of this study was to determine whether ligands that stimulate the epidermal growth factor receptor (EGFR) but do not induce its degradation are more potent activators of corneal wound healing.
Telomerase immortalized human corneal epithelial (hTCEpi) cells were grown in culture and assessed for their ability to migrate and proliferate in response to epidermal growth factor (EGF) and transforming growth factor- (TGF-). In parallel, the endocytic trafficking of the EGFR in response to these ligands was examined.
When treated with EGF, hTCEpi cells proliferated and were able to migrate. Following stimulation with TGF-, hTCEpi cells had a comparable level of proliferation, but enhanced cell migration. While both ligands initiated EGFR internalization, only those receptors that were stimulated with EGF progressed to degradation. EGFRs stimulated with TGF- recycled back to the plasma membrane.
This study reveals that ligand-stimulated down-regulation of the EGFR limits the ability of corneal epithelial cells to make the cellular changes associated with corneal wound healing. Ligands that stimulate EGFR endocytosis, but not degradation, enhance selected cellular changes associated with corneal wound healing.
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