TRPM8 Controls Melanin Synthesis in Human Skin Melanocyte

Abstract

Transient receptor potential melastatin 8 TRPM8 is the cold stimulus receptor found as a member of the temperature sensor transient receptor potential TRP family in peripheral sensory nerves. Currently, some studies about TRPM8 functions besides the temperature sensor are in progress, but little is known about the role of TRPM8 in human skin melanocytes. Therefore, we examined the function and effect of Geranium robertianum L. on TRPM8 in human skin melanocytes. As a result, mRNA expressions of melanin synthesis-related factors were decreased by this TRPM8 activator. On the other hand, a TRPM8 inhibitor exerted reverse effects. In UVB-irradiated melanocytes, TRPM8 activity and mRNA expression were decreased, and mRNA expressions of melanin synthesis-related factors were increased. Moreover, Geranium robertianum L. increased TRPM8 activity and mRNA expression, and decreased mRNA expressions of melanin synthesis-related factors in human skin melanocytes. On the basis of these results, it was concluded that TRPM8 had a suppressive function for melanin synthesis and the reduction of this function by UVB irradiation induced the acceleration of melanin synthesis in skin melanocytes. Since Geranium robertianum L. enhanced TRPM8 activity and mRNA level, it may prevent and improve pigmentation induced by the excessive synthesis of melanin.

Transient Receptor Potential channels, TRPV1 and TRPA1 in melanocytes synergize UV‐dependent and UV‐independent melanogenesis

“…Our results show that the channel‐mediated Ca 2+ signalling alone does not significantly affect melanogenesis, but synergizes other melanogenic factors. This may explain the conflicting actions of Ca 2+ in melanogenesis reported by previous studies (Bellono et al, 2013, 2014; Bellono & Oancea, 2013; Buffey et al, 1991; Choi et al, 2009; Devi et al, 2009; Maeda et al, 1992; Murakami et al, 2017; Oancea et al, 2009; Stanisz et al, 2012) and the positive effect of Ca 2+ on melanogenesis may only be observed when Ca 2+ signal crosstalks with specific melanogenic signals in some condition. Nevertheless, we provide evidence to show that Ca 2+ , at least TRPV1‐ and TRPA1‐mediated Ca 2+ influx synergizes UVA, cAMP or NO signalling pathways to stimulate melanogenesis in melanocytes.…”

“…Previous studies have shown that several calcium‐permeable ion channels in melanocytes are implicated in melanogenesis (Bellono et al, 2013, 2014; Bellono & Oancea, 2013; Devi et al, 2009; Murakami et al, 2017; Oancea et al, 2009; Stanisz et al, 2012). For example, UV radiation activates a retinal‐dependent GPCR in melanocytes, which initiates a phospholipase C (PLC) signalling cascade to activate downstream TRPA1 and induces early melanin synthesis (Bellono et al, 2013, 2014; Bellono & Oancea, 2013).…”

“…Previous studies have shown that several calcium-permeable ion channels in melanocytes are implicated in melanogenesis (Bellono et al, , 2014Devi et al, 2009;Murakami et al, 2017;Oancea et al, 2009;Stanisz et al, 2012).…”

“…Paradoxically, some studies have reported inhibitory effects of Ca 2+ on melanogenesis, complicating the role of Ca 2+ . For example, activation of Ca 2+ ‐permeable TRPM8 channels in melanocytes suppresses melanin synthesis (Murakami et al, 2017); increasing intracellular Ca 2+ by Ca 2+ ionophore decreases the activity and content of melanogenic key enzyme tyrosinase in melanocytes (Maeda et al, 1992); and decreasing intracellular Ca 2+ by a Ca 2+ chelator significantly increases melanogenesis (Buffey et al, 1991). In addition, activation of Ca 2+ ‐permeable TRPV1 channels in melanocytes does not affect melanogenesis (Choi et al, 2009).…”