Beschleunigung der kutanen Wundheilung durch transiente Inhibition von p53

Abstract

The increase of cell proliferation during early wound healing is thought to be regulated by a decrease of apoptosis. In contrast, the reduction of cellularity during final wound maturation may be controlled by an increase of apoptotic cell death. Herein we studied whether p53 is involved in wound healing-associated apoptosis, and whether transient inhibition of p53 is effective to improve the early healing process of cutaneous wounds. Using intravital microscopic and immunohistochemical techniques in hairless mice, we demonstrate that in vivo inhibition of p53 by pifithrin-alpha (PFT-α, 2.2 mg/kg ip) accelerates early epithelialisation and neovascularization of cutaneous wounds by [1] promoting leukocyte recruitment, [2] increasing cell proliferation, and [3] reducing apoptotic cell death. We further show that final wound closure with downregulation of cell proliferation is not inhibited by PFT-α treatment, indicating that transient blockade of p53 function does not affect the process of wound maturation. From our study we conclude that transient inhibition of p53 supports early cell proliferation required for rapid tissue repair, and we propose that PFT-α may thus represent an attractive approach in the treatment of delayed wound healing.