6-Formylindolo[3,2-b]Carbazole Accelerates Skin Wound Healing via Activation of ERK, but Not Aryl Hydrocarbon Receptor
| Autor: | Yoko Fuyuno, Mari Kiyomatsu, Masutaka Furue, Hiroshi Uchi, Mao Yasumatsu, Konosuke Nagae, Zhouwei Wu, Hirofumi Kai, Mary Ann Suico, Saori Morino-Koga, Chikage Mitoma |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Keratinocytes Carbazoles Dermatology Biology Biochemistry Cell Line Diabetes Mellitus Experimental 03 medical and health sciences Mice Cell Movement Animals Humans Keratinocyte migration Receptor Protein kinase A Extracellular Signal-Regulated MAP Kinases Molecular Biology Protein kinase B Skin Wound Healing integumentary system Kinase Cell Biology Aryl hydrocarbon receptor 030104 developmental biology Receptors Aryl Hydrocarbon Mice Inbred DBA biology.protein Cancer research Wound healing |
| Zdroj: | The Journal of investigative dermatology. 137(10) |
| ISSN: | 1523-1747 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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