α7-nAChR Activation Has an Opposite Effect on Healing of Covered and Uncovered Wounds.

Abstract

The α7 nicotinic acetylcholine receptor (α7-nAChR) is associated with inflammation, re-epithelialization, and angiogenesis in wound healing process. A recent study demonstrated that PNU-282987, a selective agonist of α7-nAChR, accelerates the repair of diabetic excisional wounds. Whether α7-nAChR activation promotes non-diabetic wounds healing is unknown. The aim of this study was to evaluate the effects of α7-nAChR activation on non-diabetic wound healing. The effects were evaluated in two wound models. In the first model, the wound was covered with a semi-permeable transparent dressing. In the second model, the wound was left uncovered. In both models, the mice were randomly assigned to two treatment groups: saline or PNU282987 (25 mice in each group). In covered wounds, we found that α7-nAChR activation inhibited re-epithelialization, angiogenesis, and epithelial cells proliferation, promoted neo-epithelial detachment, and suppressed neutrophil infiltration and the expression of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). However, in uncovered wounds, we observed that α7-nAChR activation promoted re-epithelialization and angiogenesis, inhibited neutrophil infiltration and the expression of high mobility group box (HMGB)-1, epidermal growth factor (EGF), and VEGF. In conclusion, this data demonstrated that α7-nAChR activation inhibited wound healing in covered wounds but played an opposite role in uncovered wounds. The opposite effect might be primarily due to inhibition of inflammation.