Activation of temperature-sensitive Ca2+-permeable TRPV3 channels by natural -hydroxyl acids causes exfoliation for skin-resurfacing

Chemical peeling has been a conventional chemical exfoliation process or cosmetic treatment that improves the appearance of the skin. Chemical peels use different types of fruit acids to cause skin to exfoliate or eventually peel off to help diminish the look of wrinkles and aging. However, the molecular mechanism underlying the exfoliation effect induced by fruit acids remains largely unknown. In this talk I will present lines of evidence that activation of temperature-sensitive Ca2+-permeable transient receptor potential vanilloid 3 (TRPV3) channels by natural �-hydroxyl acids causes exfoliation for skin-resurfacing. TRPV3 channel in keratinocytes is potently activated by intracellular acidification induced by glycolic acid. Intracellular acidification leads to direct activation of TRPV3 and promotes cell death. Site-directed mutagenesis revealed that an N-terminal histidine residue, His-426, known to be involved in 2-aminoethyl diphenylborinate-mediated TRPV3 activation, is critical for sensing intracellular proton levels. Furthermore, pharmacological activation of TRPV3 by the channel agonist natural carvacrol also induces cell death of hair follicle outer root sheath (ORS) cells, and topical application of carvacrol to mouse dorsal skin also inhibits hair growth. Taken together, our recent findings indicate that intracellular protons can strongly activate TRPV3, and TRPV3-mediated proton sensing and cell death in keratinocytes may serve as a molecular basis for the cosmetic use of AHAs and their therapeutic potential in acidic pH-related skin disorders.