Beta-adrenergic receptor agonists delay while antagonists accelerate epithelial wound healing: Evidence of an endogenous adrenergic network within the corneal epithelium

Christine Pullar, Min Zhao, Bing Song, Jin Pu, Brian Reid, Shahed Ghoghawala, Colin Darnley McCaig, R. Rivkah Isseroff

Research output: Contribution to journalArticle

35 Citations (Scopus)

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 languageEnglish
Pages (from-to)261-272
Number of pages12
JournalJournal of Cellular Physiology
Volume211
Issue number1
Early online date16 Jan 2007
DOIs
Publication statusPublished - 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

Cite this