β2-adrenergic receptor activation delays wound healing

Christine E. Pullar, Jennifer C. Grahn, Wei Liu, Roslyn Rivkah Isseroff

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Keratinocytes migrate directionally into the wound bed to initiate re-epithelialization, necessary for wound closure and restoration of barrier function. They solely express the β2-adrenergic receptor (β2-AR) subtype of β-ARs and can also synthesize β-AR agonists generating a hormonal mediator network in the skin. Emerging studies from our laboratory demonstrate that β-AR agonists decrease keratinocyte migration via a protein phosphatase (PP) 2A-dependent mechanism. Here we have extended our investigations to observe the effects of β2-AR activation on keratinocyte polarization, migration, and ERK phosphorylation at the wound edge, cytoskeletal organization, phospho-ERK intracellular localization, proliferation, human skin wound re-epithelialization, wound-induced ERK phosphorylation, and murine skin wound healing. We demonstrate that in keratinocytes, β2-AR activation is anti-motogenic and anti-mitogenic with both mechanisms being PP2A dependent, β2-AR activation dramatically alters the organization of the actin cytoskeleton and prevents localization of phospho-ERK to the lamellipodial edge and its colocalization with vinculin. Finally, we demonstrate a β2-AR-mediated delay in re-epithelialization and decrease in wound-induced epidermal ERK phosphorylation in human skin wounds and a delay in re-epithelialization in murine tail-clip wounds. Our work uncovers novel keratinocyte biology and a previously unrecognized role for the adrenergic hormonal mediator network in the wound repair process.

Original languageEnglish (US)
Pages (from-to)76-86
Number of pages11
JournalFASEB Journal
Volume20
Issue number1
DOIs
StatePublished - Jan 2006

Keywords

  • ERK activation
  • Focal adhesions
  • Keratinocyte migration
  • Wound re-epithelialization

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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