Scholarlink

<p>Vitiligo is an acquired depigmenting disorder characterized by progressive melanocyte loss, yet its cellular mechanisms remain incompletely understood. Here, we identify a melanocyte dedifferentiation-like shift as a potentially reversible pathogenic mechanism. In healthy skin, melanocytes reside within a basement membrane niche defined by dystroglycan-laminin-211 adhesion. In vitiligo, extracellular matrix remodeling with reduced laminin-211 and increased laminin-332 is associated with a shift toward integrin α3β1-laminin-332 interactions. This alteration correlates with melanocyte dedifferentiation-like changes, together with Rho-F-actin remodeling, and coordinated alterations in Hippo, MAPK, and c-Jun signaling. Affected melanocytes exhibit reduced pigmentation and features of neural crest-like states, including multilineage potential. Importantly, these changes are partially reversible. Pharmacological modulation restored melanocyte differentiation and pigmentation in mouse models and ex vivo human skin, with JAK inhibition also promoting redifferentiation. These findings identify a microenvironment-driven mechanism in vitiligo and suggest potential therapeutic strategies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Aberrant laminin signaling drives melanocyte dedifferentiation and unveils a tractable therapeutic target in vitiligo

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月17日

查看全文
  • Fei Yang,
  • Lingli Yang,
  • Sylvia Lai,
  • Masafumi Yokota,
  • Yasutaka Kuroda,
  • Takuo Yuki,
  • Yoshito Takahashi,
  • Tetsuya Sayo,
  • Takeshi Namiki,
  • Hiroyuki Goto,
  • Sho Hiroyasu,
  • Shigetoshi Sano,
  • Shintaro Inoue,
  • Yoichi Mizukami,
  • Daisuke Tsuruta,
  • Ichiro Katayama

摘要

Vitiligo is an acquired depigmenting disorder characterized by progressive melanocyte loss, yet its cellular mechanisms remain incompletely understood. Here, we identify a melanocyte dedifferentiation-like shift as a potentially reversible pathogenic mechanism. In healthy skin, melanocytes reside within a basement membrane niche defined by dystroglycan-laminin-211 adhesion. In vitiligo, extracellular matrix remodeling with reduced laminin-211 and increased laminin-332 is associated with a shift toward integrin α3β1-laminin-332 interactions. This alteration correlates with melanocyte dedifferentiation-like changes, together with Rho-F-actin remodeling, and coordinated alterations in Hippo, MAPK, and c-Jun signaling. Affected melanocytes exhibit reduced pigmentation and features of neural crest-like states, including multilineage potential. Importantly, these changes are partially reversible. Pharmacological modulation restored melanocyte differentiation and pigmentation in mouse models and ex vivo human skin, with JAK inhibition also promoting redifferentiation. These findings identify a microenvironment-driven mechanism in vitiligo and suggest potential therapeutic strategies.