6-Formylindolo[3,2-b]Carbazole Accelerates Skin Wound Healing via Activation of ERK, but Not Aryl Hydrocarbon Receptor

Saori Morino-Koga, Hiroshi Uchi, Chikage Mitoma, Zhouwei Wu, Mari Kiyomatsu, Yoko Fuyuno, Konosuke Nagae, Mao Yasumatsu, Mary Ann Suico, Hirofumi Kai, Masutaka Furue

研究成果: ジャーナルへの寄稿記事

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Wound healing is an elaborate process composed of overlapping phases, such as proliferation and remodeling, and is delayed in several circumstances, including diabetes. Although several treatment strategies for chronic wounds, such as growth factors, have been applied, further alternatives are required. The skin, especially keratinocytes, is continually exposed to UV rays, which impairs wound healing. 6-Formylindolo[3,2-b]carbazole (FICZ) is a tryptophan photoproduct formed by UV exposure, indicating that FICZ might be one of the effectors of UV radiation. In contrast, treatment with tryptophan, the precursor for FICZ, promoted wound closure in keratinocytes. Therefore, the aim of our study was to determine the role of FICZ in wound healing. Here we showed that FICZ enhanced keratinocyte migration through mitogen-activated protein kinase/extracellular signal-regulated kinase activation, and promoted wound healing in various mouse models, including db/db mice, which exhibit wound healing impairments because of type 2 diabetes. Moreover, FICZ, the endogenous ligand of an aryl hydrocarbon receptor, accelerated migration even in the aryl hydrocarbon receptor knockdown condition and also promoted wound healing in DBA/2 mice, bearing a low-affinity aryl hydrocarbon receptor, suggesting that FICZ enhanced keratinocyte migration in a mitogen-activated protein kinase/extracellular signal-regulated kinase-dependent, but aryl hydrocarbon receptor-independent, manner. The function of FICZ might indicate the possibility of its clinical use for intractable chronic wounds.

元の言語英語
ページ(範囲)2217-2226
ページ数10
ジャーナルJournal of Investigative Dermatology
137
発行部数10
DOI
出版物ステータス出版済み - 10 2017

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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