GPNMB is expressed in human epidermal keratinocytes but disappears in the vitiligo lesional skin

Abstract

AbstractGPNMB is involved in multiple cellular functions including cell adhesion, stress protection and stem cell maintenance. In skin, melanocyte-GPNMB is suggested to mediate pigmentation through melanosome formation, but details of keratinocyte-GPNMB have yet to be well understood. We confirmed the expression of GPNMB in normal human epidermal keratinocytes (NHEKs) by reducing the expression using siRNA. A higher calcium concentration of over 1.25 mM decreased the GPNMB expression. Histological staining showed that GPNMB was expressed in the basal layer of normal skins but completely absent in vitiligo skins. The normal expression of GPNMB in nevus depigmentosus skin suggested that lack of GPNMB is characteristic of vitiligo lesional skins. IFN-γ and IL-17A, two cytokines with possible causal roles in vitiligo development, inhibited GPNMB expression in vitro. Approximately 4–8% of the total GPNMB expressed on NHEKs were released possibly by ADAM 10 as a soluble form, but the process of release was not affected by the cytokines. The suppressive effect of IFN-γ on GPNMB was partially via IFN-γ/JAK2/STAT1 signaling axis. Decreased GPNMB expression in keratinocytes may affect melanocyte maintenance or survival against oxidative stress although further studies are needed. These findings indicate a new target for vitiligo treatment, focusing on the novel role of IFN-γ and IL-17 in downregulating keratinocyte-GPNMB.