The glycoprotein GPNMB protects against oxidative stress through enhanced PI3K/AKT signaling in epidermal keratinocytes.

ABSTRACT: Vitiligo, an autoimmune disease caused by environmental and genetic factors, is characterized by the specific loss of epidermal melanocytes (MCs). IFN-γ, predominantly derived from MC-targeting CD8⁺ T cells, plays a key role in vitiligo pathogenesis. Previously, we found that glycoprotein nonmetastatic melanoma protein B (GPNMB) is specifically lost in the basal epidermal layer of vitiligo lesions and downregulated by IFN-γ in normal human epidermal keratinocytes (KCs) (NHEKs). This study aimed to determine the role of KC GPNMB in normal and vitiligo epidermis and demonstrated that GPNMB plays a protective role against H₂O₂-induced oxidative stress due to its extracellular domain. In contrast, the NRF2/KEEP1 system was not involved in the anti-oxidative res

SUBMITTER: Nishida N 

PROVIDER: S-EPMC11930081 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature