Thermo- and chemosensory cation channel TRPV1: a novel target for skin anti-aging

Abstract

Transient receptor potential vanilloid 1 (TRPV1) is a member of the non-selective cationic channel family. TRPV1 is activated by capsaicin, heat, ultraviolet (UV), and acid, and its activation results in an influx of divalent and monovalent cations such as Ca2+, Na+, and Mg2+ ions. TRPV1 channel is expressed not only in neuronal cells in the brain, but also in keratinocytes in the epidermis. Recent studies suggested that TRPV1 regulates the heat- and UV-induced matrix metalloproteinases-1 (MMP-1) expression in human keratinocytes in vitro. In addition, the expression level of TRPV1 proteins was increased by heat and UV stimulus in human skin in vivo. However, little is known about the initial mechanism of UV-induced TRPV1 activation. It is important to study the initial activation mechanism of TRPV1 by UV irradiation in order to identify the precise role of TRPV1 in UV-induced responses. In the present study, I investigated how UV can activate TRPV1 through the non-receptor protein tyrosine kinase Src in HaCaT keratinocytes. UV-irradiation induced TRPV1 and Src trafficking into cell surface membrane in HaCaT cells. This UV-induced trafficking of TRPV1 was also blocked by Src inhibition. These results suggest that UV induces TRPV1 trafficking into cell membrane through Src kinase activation, and this initial process leads to the subsequent reactions including UV-induced MMP-1 and pro-inflammatory cytokine expressions. Based on these functional role and basal mechanism of TRPV1 following photo-stimulus, TRPV1 can be a novel target for anti-skin aging. In this study, I investigated the activity of the TRPV1 inhibitory peptide (TIP) as a novel blocker for anti-skin aging, and observed the beneficial effect of TIP in UV-induced responses both in vitro and in vivo system. According to recent studies, TRPV1 may be related to intrinsic skin aging. TRPV1 protein was expressed more in the sun-protected (upper-inner arm) skin of the elderly than in that of the young. The increased TRPV1 expression in the aged skin implies that TRPV1 may be related to well-known skin conditions of the elderly, such as senile pruritus or neurogenic inflammation, as well as to the change of neuronal outgrowth by aging. In this study, it was observed that the expression patterns of several neuronal outgrowth factors including TRPV1 are changed by aging using microarray analysis from the young and aged skin. In conclusion, Src-mediated activation of epidermis-expressed TRPV1 may have a critical role in heat or UV-induced responses, and increased expression of TRPV1 and neuronal outgrowth factors in aged skin may be related to senile skin symptoms. Therefore, TIP may act as a novel anti-skin aging molecule.