Keratinocytes take part in the regulation of substance P in melanogenesis through the HPA axis

Clinical findings have shown that skin depigmentation disorder such as vitiligo may be closely associated with the release of central and peripheral substance P (SP) resulted from chronic psychological stress or sudden mental blow. But the regulatory role of SP and its receptor, tachykinin receptor in the pathogenesis of vitiligo is unclear.To investigate the function and mechanism of SP in melanogenesis.The chronic mental stress was used to explore the intrinsic association between psychological factors, SP and melanogenesis disorder. The effect of SP on melanogenesis through hypothalamic pituitary adrenocortical (HPA) axis was studied by skin culture in vitro. The conditioned medium experiment demonstrated the indirect effect of SP on melanogenesis of B16F10 cells through HaCaT cells. The ability to produce melanin was evaluated by detecting melanin and tyrosinase activity. qRT-PCR, western blotting and immunohistochemistry were used to detect the expression of related genes and proteins in melanogenesis and HPA axis.Increased SP expression and reduction of melanogenesis in the skin of mice were observed under mental stress. Melanogenesis was suppressed in the cultured human skin treated with SP due to the down-regulation of melanin-related proteins and HPA axis genes. The melanogenesis of B16F10 cells was inhibited by the conditioned medium of HaCaT cells treated with SP.Overall, these results indicate that excess SP originated from mental stress interferes with melanogenesis through keratinocytes in the skin. The HPA axis is the key downstream to perceive the SP signaling and furtherly regulate the melanogenesis.