The Beta 2-adrenergic Receptor Activates Pro-migratory and Pro-proliferative Pathways in Dermal Fibroblasts Via Divergent Mechanisms.
From: Department of Dermatology, University of California, Davis, TB 192, One Shields Avenue, CA 95616, USA. cepullar@ucdavis.edu
Journal of cell science
- Publish Date: Feb 2006
- ISSN: 0021-9533
- Volume: 119
- Issue: Pt 3
- Pages: 592-602
- Medium: Print
- Language: English
- Citation (JAMA): Pullar Christine E, Isseroff R Rivkah, et al. The Beta 2-adrenergic Receptor Activates Pro-migratory and Pro-proliferative Pathways in Dermal Fibroblasts Via Divergent Mechanisms.. J. Cell. Sci. Feb 2006;119:592-602
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 beta2-adrenergic receptors (beta2-AR) and cutaneous keratinocytes can synthesize beta-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 beta2-AR activation modulates keratinocyte migration, essential for wound re-epithelialization. Here we describe an investigation of the effects of beta2-AR activation on the dermal component of wound healing. We examined beta2-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 beta2-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. beta2-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 beta2-AR agonist responses in cutaneous cells may generate novel therapeutic approaches for the control of wound healing.
Mesh Headings (Keywords): Actins, Adrenergic Agonists, Cell Movement, Cell Proliferation, Cells, Cultured, Dermis, Fibroblasts, Focal Adhesions, Humans, Receptors, Adrenergic, beta-2, Signal Transduction, Wound Healing, src-Family Kinases
Check for Full Text / PubMed Unique Identifier (PMID): 16443756
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