Pharmacological YAP activation promotes regenerative repair of cutaneous wounds
Edyta M. Grzelak, N. G. R. Dayan Elshan, Sida Shao, Maya L. Bulos, Sean B. Joseph, Arnab K. Chatterjee, Jian Jeffrey Chen, Vân Nguyên-Trân, Peter G. Schultz, Michael J. Bollong
Abstract
Chronic cutaneous wounds remain a persistent unmet medical need that decreases life expectancy and quality of life. Here, we report that topical application of PY-60, a small-molecule activator of the transcriptional coactivator Yes-associated protein (YAP), promotes regenerative repair of cutaneous wounds in pig and human models. Pharmacological YAP activation enacts a reversible pro-proliferative transcriptional program in keratinocytes and dermal cells that results in accelerated re-epithelization and regranulation of the wound bed. These results demonstrate that transient topical administration of a YAP activating agent may represent a generalizable therapeutic approach to treating cutaneous wounds.