title: Deletion of the α2A/α2C-adrenoceptors accelerates cutaneous wound healing in mice.
abstract: The α2-adrenoceptors regulate the sympathetic nervous system, controlling presynaptic catecholamine release. However, the role of the α2-adrenoceptors in cutaneous wound healing is poorly understood. Mice lacking both the α2A/α2C-adrenoceptors were used to evaluate the participation of the α2-adrenoceptor during cutaneous wound healing. A full-thickness excisional lesion was performed on the dorsal skin of the α2A/α2C-adrenoceptor knockout and wild-type mice. Seven or fourteen days later, the animals were euthanized and the lesions were formalin-fixed and paraffin-embedded or frozen. Murine skin fibroblasts were also isolated from α2A/α2C-adrenoceptor knockout and wild-type mice, and fibroblast activity was evaluated. The in vivo study demonstrated that α2A/α2C-adrenoceptor depletion accelerated wound contraction and re-epithelialization. A reduction in the number of neutrophils and macrophages was observed in the α2A/α2C-adrenoceptor knockout mice compared with wild-type mice. In addition, α2A/α2C-adrenoceptor depletion enhanced the levels of nitrite and hydroxyproline, and the protein expression of transforming growth factor-β and vascular endothelial growth factor. Furthermore, α2A/α2C-adrenoceptor depletion accelerated blood vessel formation and myofibroblast differentiation. The in vitro study demonstrated that skin fibroblasts isolated from α2A/α2C-adrenoceptor knockout mice exhibited enhanced cell migration, α-smooth muscle actin _protein expression and collagen deposition compared with wild-type skin fibroblasts. In conclusion, α2A/α2C-adrenoceptor deletion accelerates cutaneous wound healing in mice.
authors.affiliation: Department of Histology and Embryology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Romana-Souza
authors.forename: Adriana P
authors.initials: AP
authors.lastname: Nascimento
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Brum
authors.forename: Andréa
authors.initials: A
authors.lastname: Monte-Alto-Costa
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D012867:Skin / Q000294:innervation / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
chemical_list: D018341:Receptors, Adrenergic, alpha-2; D042461:Vascular Endothelial Growth Factor A
keywords: collagen fibres; cutaneous wound healing; fibroblasts; knockout mice; α2A/α2C-adrenoceptors