Hippo Pathway Regulates Cell Proliferation in Skin Epidermis Exposed to Mechanical Forces

Tissue expansion is an integral component of reconstructive surgery used to promote native skin growth. This process is driven by the gradual inflation of the tissue expander placed subcutaneously on the patient's body. Despite its widespread use, the lack of in vivo evidence on the biological processes underlying skin growth has limited technological advancements. Here, we explore the gene and protein expression changes that control mechanically induced skin growth during tissue expansion. Using a porcine tissue expansion model, we revealed that skin expansion disrupts key components responsible for epithelial integrity, as evidenced by the loss of E-cadherin and alpha-catenin expression in expanded skin compared to the unexpanded control. This disruption correlates with the translocation of the transcriptional factor YAP1 from the membrane to the nucleus, activating keratinocyte proliferation and possibly regulating other critical processes involved in skin adaptation to mechanical stretch. Our data show that in vivo cell proliferation is mediated by force-induced changes in the composition of molecular complexes formed by E-cadherin, alpha-catenin, and YAP1.