title: β2-adrenoceptor activation modulates skin wound healing processes to reduce scarring.
abstract: During wound healing, excessive inflammation, angiogenesis, and differentiated human dermal fibroblast (HDF ) function contribute to scarring, whereas hyperpigmentation negatively affects scar quality. Over 100 million patients heal with a scar every year. To investigate the role of the beta 2 adrenergic receptor (β2AR) in wound scarring, the ability of beta 2 adrenergic receptor agonist (β2ARag) to alter HDF differentiation and function, wound inflammation, angiogenesis, and wound scarring was explored in HDFs, zebrafish, chick chorioallantoic membrane assay (CAM), and a porcine skin wound model, respectively. Here we identify a β2AR-mediated mechanism for scar reduction. β2ARag significantly reduced HDF differentiation, via multiple cAMP and/or fibroblast growth factor 2 or basic FGF (FGF2)-dependent mechanisms, in the presence of transforming growth factor betaβ1, reduced contractile function, and inhibited mRNA expression of a number of profibrotic markers. β2ARag also reduced inflammation and angiogenesis in zebrafish and CAMs in vivo, respectively. In Red Duroc pig full-thickness wounds, β2ARag reduced both scar area and hyperpigmentation by almost 50% and significantly improved scar quality. Indeed, mechanisms delineated in vitro and in other in vivo models were evident in the β2ARag-treated porcine scars in vivo. Both macrophage infiltration and angiogenesis were initially decreased, whereas DF function was impaired in the β2ARag-treated porcine wound bed. These data collectively reveal the potential of β2ARag to improve skin scarring.
authors: Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, UK.
authors: Gabrielle S
authors: GS
authors: Le Provost
authors: Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, UK.
authors: Christine E
authors: CE
authors: Pullar
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000378:metabolism; D002921:Cicatrix / Q000503:physiopathology*; D020405:Dermis / Q000166:cytology / Q000293:injuries; D004195:Disease Models, Animal; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018919:Neovascularization, Physiologic / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D034421:Sus scrofa; D014945:Wound Healing / Q000502:physiology*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: C553443:ADRB2 protein, human; C000595544:ADRB2 protein, zebrafish; D018343:Receptors, Adrenergic, beta-2; D029961:Zebrafish Proteins; D016222:Fibroblast Growth Factor 2