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

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

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2217-2226
Number of pages10
JournalJournal of Investigative Dermatology
Volume137
Issue number10
DOIs
Publication statusPublished - Oct 1 2017

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Aryl Hydrocarbon Receptors
Wound Healing
Skin
Chemical activation
Keratinocytes
Extracellular Signal-Regulated MAP Kinases
Medical problems
Mitogen-Activated Protein Kinases
Tryptophan
Bearings (structural)
Wounds and Injuries
Ultraviolet radiation
Intercellular Signaling Peptides and Proteins
Inbred DBA Mouse
Ligands
Type 2 Diabetes Mellitus
6-formylindolo(3,2-b)carbazole
Radiation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

6-Formylindolo[3,2-b]Carbazole Accelerates Skin Wound Healing via Activation of ERK, but Not Aryl Hydrocarbon Receptor. / Morino-Koga, Saori; Hiroshi, Uchi; Mitoma, Chikage; Wu, Zhouwei; Kiyomatsu, Mari; Fuyuno, Yoko; Nagae, Konosuke; Yasumatsu, Mao; Suico, Mary Ann; Kai, Hirofumi; Furue, Masutaka.

In: Journal of Investigative Dermatology, Vol. 137, No. 10, 01.10.2017, p. 2217-2226.

Research output: Contribution to journalArticle

Morino-Koga, S, Hiroshi, U, Mitoma, C, Wu, Z, Kiyomatsu, M, Fuyuno, Y, Nagae, K, Yasumatsu, M, Suico, MA, Kai, H & Furue, M 2017, '6-Formylindolo[3,2-b]Carbazole Accelerates Skin Wound Healing via Activation of ERK, but Not Aryl Hydrocarbon Receptor', Journal of Investigative Dermatology, vol. 137, no. 10, pp. 2217-2226. https://doi.org/10.1016/j.jid.2016.10.050
Morino-Koga, Saori ; Hiroshi, Uchi ; Mitoma, Chikage ; Wu, Zhouwei ; Kiyomatsu, Mari ; Fuyuno, Yoko ; Nagae, Konosuke ; Yasumatsu, Mao ; Suico, Mary Ann ; Kai, Hirofumi ; Furue, Masutaka. / 6-Formylindolo[3,2-b]Carbazole Accelerates Skin Wound Healing via Activation of ERK, but Not Aryl Hydrocarbon Receptor. In: Journal of Investigative Dermatology. 2017 ; Vol. 137, No. 10. pp. 2217-2226.
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AU - Mitoma, Chikage

AU - Wu, Zhouwei

AU - Kiyomatsu, Mari

AU - Fuyuno, Yoko

AU - Nagae, Konosuke

AU - Yasumatsu, Mao

AU - Suico, Mary Ann

AU - Kai, Hirofumi

AU - Furue, Masutaka

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