Abstract
Wound healing is a complex and well-orchestrated biological process. Corneal epithelial cells (CECs) must respond quickly to trauma to rapidly restore barrier function and protect the eye from noxious agents. They express a high level of beta 2-adrenergic receptors but their function is unknown. Here, we report the novel finding that they form part of a regulatory network in the corneal epithelium, capable of modulating corneal epithelial wound repair. beta-adrenergic receptor agonists delay CEC migration via a protein phosphatase 2A-mediated mechanism and decrease both electric field-directed migration and corneal wound healing. Conversely, B-adrenergic receptor antagonists accelerate CEC migration, enhance electric field-mediated directional migration, and promote corneal wound repair. We demonstrate that CECs express key enzymes required for epinephrine (beta-adrenergic receptor agonist) synthesis in the cytoplasm and can detect epinephrine in cell extracts. We propose that the mechanism for the pro-motogenic effect of the beta-adrenergic antagonist is blockade of the beta 2-adrenergic receptor preventing autocrine catecholamine binding. Further investigation of this network will improve our understanding of one of the most frequently prescribed class of drugs.
Original language | English |
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Pages (from-to) | 261-272 |
Number of pages | 12 |
Journal | Journal of Cellular Physiology |
Volume | 211 |
Issue number | 1 |
Early online date | 16 Jan 2007 |
DOIs | |
Publication status | Published - Apr 2007 |
Keywords
- human epidermal-keratinocytes
- physiological electric-field
- protein phosphatase 2A
- directed migration
- cell-migration
- okadaic acid
- map kinase
- catecholamine biosynthesis
- sympathetic-stimulation
- directional migration