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PLoS One ; 6(9): e25215, 2011.
Article in English | MEDLINE | ID: mdl-21949884

ABSTRACT

Cutaneous wound healing is a normal physiological process and comprises different phases. Among these phases, angiogenesis or new blood vessel formation in wound tissue plays an important role. Skin is richly supplied by sympathetic nerves and evidences indicate the significant role of the sympathetic nervous system in cutaneous wound healing. Dopamine (DA) is an important catecholamine neurotransmitter released by the sympathetic nerve endings and recent studies have demonstrated the potent anti-angiogenic action of DA, which is mediated through its D(2) DA receptors. We therefore postulate that this endogenous catecholamine neurotransmitter may have a role in the neovascularization of dermal wound tissues and subsequently in the process of wound healing. In the present study, the therapeutic efficacy of D(2) DA receptor antagonist has been investigated for faster wound healing in a murine model of full thickness dermal wound. Our results indicate that treatment with specific D(2) DA receptor antagonist significantly expedites the process of full thickness normal dermal wound healing in mice by inducing angiogenesis in wound tissues. The underlined mechanisms have been attributed to the up-regulation of homeobox transcription factor HoxD3 and its target α5ß1 integrin, which play a pivotal role in wound angiogenesis. Since D(2) DA receptor antagonists are already in clinical use for other disorders, these results have significant translational value from the bench to the bedside for efficient wound management along with other conventional treatment modalities.


Subject(s)
Dermis/blood supply , Dermis/injuries , Dopamine/pharmacology , Neovascularization, Physiologic/drug effects , Neovascularization, Physiologic/physiology , Wound Healing/physiology , Wounds and Injuries/prevention & control , Animals , Blotting, Western , Cells, Cultured , DNA-Binding Proteins/metabolism , Dermis/drug effects , Dopamine Agents/pharmacology , Dopamine Antagonists/pharmacology , Dopamine D2 Receptor Antagonists , Endothelium, Vascular/cytology , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Flow Cytometry , Integrin alpha5beta1/metabolism , Mice , Receptors, Dopamine D2/metabolism , Salicylamides/pharmacology , Umbilical Veins/cytology , Umbilical Veins/drug effects , Umbilical Veins/metabolism , Wounds and Injuries/pathology
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