Abstract | PURPOSE: METHODS: Kinetic analysis and dose response curves were performed by using in vitro and in vivo wound-healing assays. Biochemical assays were used to determine receptor expression and activity. Human tears were collected and quantitatively analyzed by multianalyte profiling for endogenous EGFR ligands. RESULTS: CONCLUSIONS: Under unwounded conditions, only EGF was present at concentrations near the ligand's Kd for the receptor, indicating it is the primary mediator of corneal epithelial homeostasis. Other ligands were present but at concentrations 11- to 7500-fold less their Kd, preventing significant ligand binding. Further, the high levels of EGF and its predicted binding preclude receptor occupancy by exogenous ligand and can explain the discrepancy between the in vitro and in vivo data. Therefore, therapeutic use of EGFR ligands may be unpredictable and impractical.
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Authors | Joanne L Peterson, Eric D Phelps, Mark A Doll, Shlomit Schaal, Brian P Ceresa |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 55
Issue 5
Pg. 2870-80
(May 01 2014)
ISSN: 1552-5783 [Electronic] United States |
PMID | 24722692
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
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Topics |
- Adult
- Animals
- Cells, Cultured
- Epithelial Cells
(drug effects)
- Epithelium, Corneal
(physiology)
- ErbB Receptors
(physiology)
- Female
- Homeostasis
(physiology)
- Humans
- Ligands
- Male
- Mice
- Mice, Inbred C57BL
- Middle Aged
- Models, Biological
- Tears
(metabolism)
- Wound Healing
(drug effects, physiology)
- Young Adult
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