期刊
FASEB JOURNAL
卷 20, 期 1, 页码 76-86出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.05-4188com
关键词
wound re-epithelialization; ERK activation; keratinocyte migration; focal adhesions
资金
- NIAMS NIH HHS [AR 44518, AR 48827] Funding Source: Medline
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR044518, K01AR048827] Funding Source: NIH RePORTER
Keratinocytes migrate directionally into the wound bed to initiate re-epithelialization, necessary for wound closure and restoration of barrier function. They solely express the beta 2-adrenergic receptor (beta 2-AR) subtype of beta-ARs and can also synthesize beta-AR agonists generating a hormonal mediator network in the skin. Emerging studies from our laboratory demonstrate that beta-AR agonists decrease keratinocyte migration via a protein phosphatase (PP) 2A-dependent mechanism. Here we have extended our investigations to observe the effects of beta 2-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, beta 2-AR activation is antimotogenic and anti-mitogenic with both mechanisms being PP2A dependent. beta 2-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 beta 2-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. beta 2-Adrenergic receptor activation delays wound healing.
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