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β2‐Adrenergic receptor activation delays wound healing
Author(s) -
Pullar Christine E.,
Grahn Jennifer C.,
Liu Wei,
Isseroff R. Rivkah
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4188com
Subject(s) - wound healing , mapk/erk pathway , microbiology and biotechnology , keratinocyte , cell migration , phosphorylation , lysophosphatidic acid , mediator , receptor , cytoskeleton , chemistry , biology , cancer research , cell culture , cell , immunology , biochemistry , genetics
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 antimotogenic 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.— Pullar, C. E., Grahn, J. C., Liu, W., Isseroff, R. R. β2‐Adrenergic receptor activation delays wound healing. FASEB J. 20, 76 −86 (2006)