Pharmacological YAP activation promotes regenerative repair of cutaneous wounds

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 120; no. 28; p. e2305085120
• Main Authors: Grzelak, Edyta M, Elshan, N G R Dayan, Shao, Sida, Bulos, Maya L, Joseph, Sean B, Chatterjee, Arnab K, Chen, Jian Jeffrey, Nguyên-Trân, Vân, Schultz, Peter G, Bollong, Michael J
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 11-07-2023
• Subjects: Administration, Cutaneous; Animal models; Animals; Biological Sciences; Humans; Keratinocytes; Keratinocytes - metabolism; Life expectancy; Life span; Pharmacology; Quality of Life; Skin - injuries; Swine; Topical application; Wound healing; Wound Healing - physiology; Yes-associated protein; YAP activator; wound healing; keratinocyte; regenerative medicine
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2305085120

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.