The β2-adrenergic receptor activates pro-migratory and pro-proliferative pathways in dermal fibroblasts via divergent mechanisms

Christine E. Pullar, Roslyn Rivkah Isseroff

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Dermal fibroblasts are required for skin wound repair; they migrate into the wound bed, proliferate, synthesize extracellular matrix components and contract the wound. Although fibroblasts express (32-adrenergic receptors (β2-AR) and cutaneous keratinocytes can synthesize β-AR agonists (catecholamines), the functional significance of this hormonal mediator network in the skin has not been addressed. Emerging studies from our laboratory demonstrate that β2-AR activation modulates keratinocyte migration, essential for wound re-epithelialization. Here we describe an investigation of the effects of β2-AR activation on the dermal component of wound healing. We examined β2-AR-mediated regulation of biological processes in dermal fibroblasts that are critical for wound repair: migration, proliferation, contractile ability and cytoskeletal conformation. We provide evidence for the activation of at least two divergent β2-AR-mediated signaling pathways in dermal fibroblasts, a Src-dependent pro-migratory pathway, transduced through the epidermal growth factor receptor and extracellular signal-regulated kinase, and a PKA-dependent pro-proliferative pathway. β2-AR activation attenuates collagen gel contraction and alters the actin cytoskeleton and focal adhesion distribution through PKA-dependent mechanisms. Our work uncovers a previously unrecognized role for the adrenergic hormonal mediator network in the cutaneous wound repair process. Exploiting these divergent β2-AR agonist responses in cutaneous cells may generate novel therapeutic approaches for the control of wound healing.

Original languageEnglish (US)
Pages (from-to)592-602
Number of pages11
JournalJournal of Cell Science
Volume119
Issue number3
DOIs
StatePublished - Feb 1 2006

Keywords

  • CAMP
  • EGFR transactivation
  • Motility
  • Skin
  • Src
  • Wound healing

ASJC Scopus subject areas

  • Cell Biology

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