Pharmacological YAP activation promotes regenerative repair of cutaneous wounds.
Edyta M GrzelakN G R Dayan ElshanSida ShaoMaya L BulosSean B JosephArnab K ChatterjeeJian Jeffrey ChenVân Nguyên-TrânPeter G SchultzMichael J BollongPublished in: Proceedings of the National Academy of Sciences of the United States of America (2023)
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.
Keyphrases
- wound healing
- small molecule
- stem cells
- mesenchymal stem cells
- cell therapy
- gene expression
- induced apoptosis
- endothelial cells
- healthcare
- signaling pathway
- quality improvement
- tissue engineering
- immune response
- heat shock
- oxidative stress
- nuclear factor
- subarachnoid hemorrhage
- inflammatory response
- pluripotent stem cells
- protein protein
- endoplasmic reticulum stress
- brain injury