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Deletion of the α2 A /α2 C ‐adrenoceptors accelerates cutaneous wound healing in mice
Author(s) -
RomanaSouza Bruna,
Nascimento Adriana P.,
Brum Patricia C.,
MonteAltoCosta Andréa
Publication year - 2014
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/iep.12093
Subject(s) - wound healing , knockout mouse , fibroblast , myofibroblast , wild type , receptor , chemistry , endocrinology , adrenergic receptor , in vivo , hydroxyproline , medicine , biology , in vitro , immunology , fibrosis , biochemistry , gene , mutant , microbiology and biotechnology
Summary 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 α2 A /α2 C ‐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 α2 A /α2 C ‐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 α2 A /α2 C ‐adrenoceptor knockout and wild‐type mice, and fibroblast activity was evaluated. The in vivo study demonstrated that α2 A /α2 C ‐adrenoceptor depletion accelerated wound contraction and re‐epithelialization. A reduction in the number of neutrophils and macrophages was observed in the α2 A /α2 C ‐adrenoceptor knockout mice compared with wild‐type mice. In addition, α2 A /α2 C ‐adrenoceptor depletion enhanced the levels of nitrite and hydroxyproline, and the protein expression of transforming growth factor‐β and vascular endothelial growth factor. Furthermore, α2 A /α2 C ‐adrenoceptor depletion accelerated blood vessel formation and myofibroblast differentiation. The in vitro study demonstrated that skin fibroblasts isolated from α2 A /α2 C ‐adrenoceptor knockout mice exhibited enhanced cell migration, α‐smooth muscle actin _protein expression and collagen deposition compared with wild‐type skin fibroblasts. In conclusion, α2 A /α2 C ‐adrenoceptor deletion accelerates cutaneous wound healing in mice.