Thermo-Sensitive Barrier : The Importance of Transient Receptor Potential Vanilloid 4 (TRPV4) in Epidermal Barrier Function

Abstract

Our skin temperature varies considerably according to the external temperature. However, very little is known about the mechanism by which temperature fluctuation directly affects the skin's physiological function. The present study provides a molecular-level explanation for the direct involvement of temperature in human skin barrier function via thermo-sensitive TRPV4 which is activated by warm temperature (>30°C) . We demonstrated that activation of TRPV4 was crucial for barrier formation and recovery, both of which were critical for the prevention of excessive dehydration of human skin keratinocytes. TRPV4 activation by physiological skin temperature (33°C) or 4α-PDD allowed influx of Ca²⁺ from extracellular spaces which promoted small GTPase Rho activation and cell-cell junction development. These changes resulted in augmentation of intercellular barrier integrity in vitro and ex vivo. Furthermore, lagerstroemia speciosa extract induced an increase in cytosolic Ca²⁺ concentrations in HEK293 cells expressing TRPV4 channels and promoted intercellular barrier function in NHEKs. We believe that our new findings will not only open a new direction for dermatological research focusing on temperature, but also lead to development of novel ideas for a new category of skin care products that take into consideration the effects of skin temperature and thermo-sensitive proteins.