Aryl hydrocarbon receptor activation restores filaggrin expression via OVOL1 in atopic dermatitis
Open accessAbstract
Filaggrin ( FLG ) mutation is a well-confirmed genetic aberration in atopic dermatitis (AD). Genome-wide association studies on AD have revealed other susceptibility genes, for example, Ovo-like 1 (OVOL1). Nonetheless, the relation between FLG and OVOL1 is unclear. Because aryl hydrocarbon receptor (AHR; a ligand-activated transcription factor), plays a role in FLG expression in keratinocytes, we hypothesized that AHR regulates FLG expression via OVOL1. To demonstrate this mechanism, we analyzed FLG expression in OVOL1-overexpressing or OVOL1-knockdown normal human epidermal keratinocytes (NHEKs). Furthermore, we tested whether AHR activation by 6-formylindolo(3,2-b)carbazole (FICZ), an endogenous AHR ligand, or Glyteer, clinically used soybean tar, upregulates FLG and OVOL1 expression in NHEKs. We found that (1) OVOL1 regulates FLG expression; (2) AHR activation upregulates OVOL1; and (3) AHR activation upregulates FLG via OVOL1. Moreover, nuclear translocation of OVOL1 was less pronounced in AD skin compared with normal skin. IL-4-treated NHEKs, an in vitro AD skin model, also showed inhibition of the OVOL1 nuclear translocation, which was restored by FICZ and Glyteer. Thus, targeting the AHR–OVOL1–FLG axis may provide new therapeutics for AD.
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β-actin (ACTB) was used as a control housekeeping gene because its gene expression is not affected by AHR ligation.
“We used β-actin (ACTB) as a control housekeeping gene, because its gene expression is not affected by AHR ligation [18,35].”
From Antioxidant Artemisia princeps Extract Enhances the Expression of Filaggrin and Loricrin via the AHR/OVOL1 Pathway (2017) · cites this paper as [18]
The Materials and Methods section (Quantitative reverse transcription-PCR analysis; page not provided) says mRNA levels were normalized to β-actin, supporting its use as a control gene. The paper does not state or demonstrate that ACTB gene expression is unaffected by AHR ligation; that reason for choosing it is not supported. (LLM, conf=0.86)
Experimental — accuracy not yet measuredLigation of AHR activates OVOL1, which induces FLG and LOR expression.
“A recent study has also clarified that the ligation of AHR activates the downstream transcription factor OVO-like 1 (OVOL1), which then induces FLG and LOR expression [18].”
From Antioxidant Artemisia princeps Extract Enhances the Expression of Filaggrin and Loricrin via the AHR/OVOL1 Pathway (2017) · cites this paper as [18]
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- Authors
- Tsuji, G., Hashimoto-Hachiya, A., Kiyomatsu-Oda, M., Takemura, M., Ohno, F., Ito, T., Morino-Koga, S., Mitoma, C., Nakahara, T., Uchi, H., & Furue, M.
- Affiliations
- Kyushu University (JP)
- Corresponding author
- Tsuji, Gaku
- ORCID
- Venue
- Cell Death & Disease
- Published
- 2017-07-13
- Volume
- 8
- Issue
- 7
- Pages
- e2931-e2931
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC5550867
- OpenAlex
- W2735723644
- Cited by
- 149
- References
- 25
- Citations by year
- 2026: 23 · 2025: 13 · 2024: 17 · 2023: 21 · 2022: 18 · 2021: 12 · 2020: 17 · 2019: 10 · 2018: 15 · 2017: 3
- FWCI
- 13.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cell Death and Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Japan Agency for Medical Research and Development
- Ministry of Health, Labour and Welfare
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and rare skin diseases.
- Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
- Keywords
- aryl hydrocarbon receptor, OVOL1, filaggrin, atopic dermatitis, keratinocytes, FICZ, IL-4, nuclear translocation, skin barrier, transcriptional regulation
- MeSH terms
- Filaggrin Proteins, Carbazoles, Cell Line, Cell Nucleus, Dermatitis, Atopic, DNA-Binding Proteins, Humans, Intermediate Filament Proteins, Membrane Proteins, Protein Precursors, Transglutaminases, Tars, Transcription Factors, Keratinocytes, Interleukin-4, Up-Regulation, Receptors, Aryl Hydrocarbon, Cell Culture Techniques, RNA Interference, RNA, Small Interfering
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