Selective Inhibition of β-Catenin/Co-Activator Cyclic AMP Response Element-Binding Protein-Dependent Signaling Prevents the Emergence of Hapten-Induced Atopic Dermatitis-Like Dermatitis
- Author:
Haruna MATSUDA-HIROSE
1
;
Tomoko YAMATE
;
Mizuki GOTO
;
Akira KATOH
;
Hiroyuki KOUJI
;
Yuya YAMAMOTO
;
Takashi SAKAI
;
Naoto UEMURA
;
Takashi KOBAYASHI
;
Yutaka HATANO
Author Information
- Publication Type:Original Article
- Keywords: Atopic dermatitis; Mouse; Therapy
- MeSH: Animals; Asthma; Chemokine CCL17; Cyclic AMP Response Element-Binding Protein; Cyclic AMP; Dermatitis; Dermatitis, Atopic; Fibrosis; Mast Cells; Mice; Myofibroblasts; Oxazolone; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Water
- From:Annals of Dermatology 2019;31(6):631-639
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND: The canonical Wnt/β-catenin signaling pathway is a fundamental regulatory system involved in various biological events. ICG-001 selectively blocks the interaction of β-catenin with its transcriptional co-activator cyclic AMP response element-binding protein (CBP). Recent studies have provided convincing evidence of the inhibitory effects of ICG-001 on Wnt-driven disease models, such as organ fibrosis, cancer, acute lymphoblastic leukemia, and asthma. However, the effects of ICG-001 in atopic dermatitis (AD) have not been investigated. OBJECTIVE: To investigate whether β-catenin/CBP-dependent signaling was contributed in the pathogenesis of AD and ICG-001 could be a therapeutic agent for AD. METHODS: We examined the effects of ICG-001 in an AD-like murine model generated by repeated topical application of the hapten, oxazolone (Ox). ICG-001 or vehicle alone was injected intraperitoneally every day during the development of AD-like dermatitis arising from once-daily Ox treatment. RESULTS: Ox-induced AD-like dermatitis characterized by increases in transepidermal water loss, epidermal thickness, dermal thickness accompanied by increased myofibroblast and mast cell counts, and serum levels of thymic stromal lymphopoietin and thymus and activation-regulated chemokine, and decreases in stratum corneum hydration, were virtually normalized by the treatment with ICG-001. Elevated serum levels of periostin tended to be downregulated, without statistical significance. CONCLUSION: These results suggest that β-catenin/CBP-dependent signaling might be involved in the pathogenesis of AD and could be a therapeutic target.
