인문학
사회과학
자연과학
공학
의약학
농수해양학
예술체육학
복합학
DBpia AI
AI 에이전트
AI 아이디어
AI 리더
AI 뷰어
Citeasy
크롬 서지관리 다운로드
지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
초록·키워드
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<sup>+</sup> 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 H<sub>2</sub>O<sub>2</sub>-induced oxidative stress due to its extracellular domain. In contrast, the NRF2/KEEP1 system was not involved in the anti-oxidative response in NHEKs but was active in MCs. GPNMB knockdown reduced the phosphorylation levels of AKT<sup>T308</sup> and AKT<sup>S473</sup> after H<sub>2</sub>O<sub>2</sub> treatment, accompanied by reduced Dickkopf-1 (DKK1) mRNA and protein production and decreased FOXM1 mRNA expression. These results suggested that GPNMB protects KCs from H<sub>2</sub>O<sub>2</sub>-induced cell death through enhanced PI3K/AKT signaling, and WNT/β-catenin/FOXM1 and DKK1/CKAP4/AKT pathways. Furthermore, a significant increase in thioredoxin-interacting protein (TXNIP) following GPNMB knockdown was observed, indicating the enhanced phosphorylation of JNK and p38 and suppression of WNT/β-catenin signaling. These results suggest that the decreased expression of epidermal GPNMB in vitiligo lesions triggers increased sensitivity to H<sub>2</sub>O<sub>2</sub>-induced oxidative stress and decreased WNT/β-catenin signaling, consistent with the pathological features of the vitiligo epidermis. These findings may enhance our understanding of vitiligo pathogenesis, provide insights into the reduced risk of epidermal cancers, and highlight novel targets for treatment.
인공지능 문자 인식 모델을 통해 추출된 텍스트로, 일부 오타나 오류가 포함될 수 있으나 지속적으로 개선 중입니다.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
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