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 language | English (US) |
|---|---|
| Pages (from-to) | 592-602 |
| Number of pages | 11 |
| Journal | Journal of Cell Science |
| Volume | 119 |
| Issue number | 3 |
| DOIs | |
| State | Published - Feb 1 2006 |
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Keywords
- CAMP
- EGFR transactivation
- Motility
- Skin
- Src
- Wound healing
ASJC Scopus subject areas
- Cell Biology
Cite this
The β2-adrenergic receptor activates pro-migratory and pro-proliferative pathways in dermal fibroblasts via divergent mechanisms. / Pullar, Christine E.; Isseroff, Roslyn Rivkah.
In: Journal of Cell Science, Vol. 119, No. 3, 01.02.2006, p. 592-602.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The β2-adrenergic receptor activates pro-migratory and pro-proliferative pathways in dermal fibroblasts via divergent mechanisms
AU - Pullar, Christine E.
AU - Isseroff, Roslyn Rivkah
PY - 2006/2/1
Y1 - 2006/2/1
N2 - 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.
AB - 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.
KW - CAMP
KW - EGFR transactivation
KW - Motility
KW - Skin
KW - Src
KW - Wound healing
UR - http://www.scopus.com/inward/record.url?scp=33644988355&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33644988355&partnerID=8YFLogxK
U2 - 10.1242/jcs.02772
DO - 10.1242/jcs.02772
M3 - Article
C2 - 16443756
AN - SCOPUS:33644988355
VL - 119
SP - 592
EP - 602
JO - Journal of Cell Science
JF - Journal of Cell Science
SN - 0021-9533
IS - 3
ER -