Guo Yuan, Yang Yi-Fei, Zhang Yun
Department of Dermatology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.
Department of Dermatology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Ann Med. 2025 Dec;57(1):2544880. doi: 10.1080/07853890.2025.2544880. Epub 2025 Aug 11.
Vitiligo is a depigmentation disorder with an undefined specific pathogenesis, with the autoimmune theory being a prominent etiology. Mycophenolate mofetil (MMF), a novel immunosuppressant, selectively inhibits inosine 5-monophosphate dehydrogenase (IMPDH), crucial for lymphocyte DNA synthesis. Recent research has highlighted MMF's efficacy in vitiligo treatment; however, the precise mechanism remains unclear. This study aimed to explore the therapeutic impact and mechanism of vitiligo.
We enrolled guinea pigs and C57/BL6 mice which were randomly divided into the hydroquinone group, the MMF & hydroquinone group, and the control group. Skin biopsy specimens were collected from designated areas which were stained using hematoxylin and eosin (H&E), Masson-Fontana (M-F), and immunofluorescence techniques. To elucidate the pharmacological mechanisms underlying the effects of MMF, real-time polymerase chain reaction (PCR) and western blotting analyses were performed.
A comparative analysis revealed a notable enhanced pigmentation in the MMF-conjunction group. Subsequent to MMF application, there was a significant augmentation in both the number of melanocytes within the basal layer and melanin-containing hair follicles. MMF activated tyrosinase (TYR), which had been suppressed by hydroquinone, and led to an upregulation of melanin-associated genes such as TYR, TYRP-1, MITF, and SILV. Additionally, there was an increase in WNT pathway-related proteins, including β-catenin, GSK3β, Axin2, Dkk, and Dact2. MMF effectively mitigated the vitiligo-like increase in IFN-γ induced by hydroquinone safely.
MMF exhibits a notable capacity to ameliorate the pigment-loss effect associated with hydroquinone through the activation of the WNT signaling pathway. Consequently, MMF emerges as a promising therapeutic agent for mitigating skin pigmentation.
白癜风是一种色素脱失性疾病，其具体发病机制尚不明确，自身免疫理论是主要病因。霉酚酸酯（MMF）是一种新型免疫抑制剂，可选择性抑制对淋巴细胞DNA合成至关重要的肌苷5-单磷酸脱氢酶（IMPDH）。近期研究凸显了MMF在白癜风治疗中的疗效；然而，确切机制仍不清楚。本研究旨在探讨MMF对白癜风的治疗作用及机制。
选取豚鼠和C57/BL6小鼠，随机分为氢醌组、MMF与氢醌联合组和对照组。从指定区域采集皮肤活检标本，采用苏木精-伊红（H&E）染色、Masson-Fontana（M-F）染色和免疫荧光技术进行染色。为阐明MMF作用的药理机制，进行了实时聚合酶链反应（PCR）和蛋白质印迹分析。
对比分析显示，MMF联合组色素沉着显著增强。应用MMF后，基底层黑素细胞数量和含黑素的毛囊数量均显著增加。MMF激活了被氢醌抑制的酪氨酸酶（TYR），并导致TYR、TYRP-1、MITF和SILV等黑素相关基因上调。此外，WNT通路相关蛋白包括β-连环蛋白、GSK3β、Axin2、Dkk和Dact2也有所增加。MMF有效且安全地减轻了氢醌诱导的白癜风样IFN-γ增加。
MMF通过激活WNT信号通路，具有显著改善与氢醌相关色素脱失效应的能力。因此，MMF有望成为减轻皮肤色素沉着的治疗药物。
