β2-adrenergic receptor activation delays wound healing

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

Research output: Contribution to journalArticle

68 Citations (Scopus)

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

Fingerprint

adrenergic receptors
tissue repair
animal injuries
Wound Healing
Adrenergic Receptors
Re-Epithelialization
Chemical activation
Phosphorylation
Skin
keratinocytes
Keratinocytes
Wounds and Injuries
skin (animal)
phosphorylation
Vinculin
Protein Phosphatase 2
agonists
Adrenergic Agents
Restoration
Actins

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

Cite this

β2-adrenergic receptor activation delays wound healing. / Pullar, Christine E.; Grahn, Jennifer C.; Liu, Wei; Isseroff, Roslyn Rivkah.

In: FASEB Journal, Vol. 20, No. 1, 01.2006, p. 76-86.

Research output: Contribution to journalArticle

Pullar, Christine E. ; Grahn, Jennifer C. ; Liu, Wei ; Isseroff, Roslyn Rivkah. / β2-adrenergic receptor activation delays wound healing. In: FASEB Journal. 2006 ; Vol. 20, No. 1. pp. 76-86.
@article{d44e18ee28c349a09256a8ca41ea40c3,
title = "β2-adrenergic receptor activation delays wound healing",
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.",
keywords = "ERK activation, Focal adhesions, Keratinocyte migration, Wound re-epithelialization",
author = "Pullar, {Christine E.} and Grahn, {Jennifer C.} and Wei Liu and Isseroff, {Roslyn Rivkah}",
year = "2006",
month = "1",
doi = "10.1096/fj.05-4188com",
language = "English (US)",
volume = "20",
pages = "76--86",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "1",

}

TY - JOUR

T1 - β2-adrenergic receptor activation delays wound healing

AU - Pullar, Christine E.

AU - Grahn, Jennifer C.

AU - Liu, Wei

AU - Isseroff, Roslyn Rivkah

PY - 2006/1

Y1 - 2006/1

N2 - 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.

AB - 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.

KW - ERK activation

KW - Focal adhesions

KW - Keratinocyte migration

KW - Wound re-epithelialization

UR - http://www.scopus.com/inward/record.url?scp=30744433667&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=30744433667&partnerID=8YFLogxK

U2 - 10.1096/fj.05-4188com

DO - 10.1096/fj.05-4188com

M3 - Article

VL - 20

SP - 76

EP - 86

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 1

ER -