The KEAP1/NRF2 Signaling Pathway in Keratinization
Keratinization is a tissue adaptation, but aberrant keratinization is associated with skin disorders such as ichthyoses, atopic dermatitis, psoriasis, and acne. The disease phenotype stems from the interaction between genes and the environment; therefore, an understanding of the adaptation machinery...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/8/751 |
| _version_ | 1797558174854676480 |
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| author | Yosuke Ishitsuka Tatsuya Ogawa Dennis Roop |
| author_facet | Yosuke Ishitsuka Tatsuya Ogawa Dennis Roop |
| author_sort | Yosuke Ishitsuka |
| collection | DOAJ |
| description | Keratinization is a tissue adaptation, but aberrant keratinization is associated with skin disorders such as ichthyoses, atopic dermatitis, psoriasis, and acne. The disease phenotype stems from the interaction between genes and the environment; therefore, an understanding of the adaptation machinery may lead to a new appreciation of pathomechanisms. The KEAP1/NRF2 signaling pathway mediates the environmental responses of squamous epithelial tissue. The unpredicted outcome of the <i>Keap1</i>-null mutation in mice allowed us to revisit the basic principle of the biological process of keratinization: sulfur metabolism establishes unparalleled cytoprotection in the body wall of terrestrial mammals. We summarize the recent understanding of the KEAP1/NRF2 signaling pathway, which is a thiol-based sensor-effector apparatus, with particular focuses on epidermal differentiation in the context of the gene-environment interaction, the structure/function principles involved in KEAP1/NRF2 signaling, lessons from mouse models, and their pathological implications. This synthesis may provide insights into keratinization, which provides physical insulation and constitutes an essential innate integumentary defense system. |
| first_indexed | 2024-03-10T17:26:44Z |
| format | Article |
| id | doaj.art-b9d9aa5651274b23a8332b093e07ce3a |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T17:26:44Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-b9d9aa5651274b23a8332b093e07ce3a2023-11-20T10:09:59ZengMDPI AGAntioxidants2076-39212020-08-019875110.3390/antiox9080751The KEAP1/NRF2 Signaling Pathway in KeratinizationYosuke Ishitsuka0Tatsuya Ogawa1Dennis Roop2Department of Dermatology, Faculty of Medicine, University of Tsukuba 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, JapanDepartment of Dermatology, Faculty of Medicine, University of Tsukuba 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, JapanDepartment of Dermatology and Charles C. Gates Center for Regenerative Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USAKeratinization is a tissue adaptation, but aberrant keratinization is associated with skin disorders such as ichthyoses, atopic dermatitis, psoriasis, and acne. The disease phenotype stems from the interaction between genes and the environment; therefore, an understanding of the adaptation machinery may lead to a new appreciation of pathomechanisms. The KEAP1/NRF2 signaling pathway mediates the environmental responses of squamous epithelial tissue. The unpredicted outcome of the <i>Keap1</i>-null mutation in mice allowed us to revisit the basic principle of the biological process of keratinization: sulfur metabolism establishes unparalleled cytoprotection in the body wall of terrestrial mammals. We summarize the recent understanding of the KEAP1/NRF2 signaling pathway, which is a thiol-based sensor-effector apparatus, with particular focuses on epidermal differentiation in the context of the gene-environment interaction, the structure/function principles involved in KEAP1/NRF2 signaling, lessons from mouse models, and their pathological implications. This synthesis may provide insights into keratinization, which provides physical insulation and constitutes an essential innate integumentary defense system.https://www.mdpi.com/2076-3921/9/8/751gene expression regulationenvironmental responsesquamous epitheliumKEAP1/NRF2 signalingkeratinizationthiol |
| spellingShingle | Yosuke Ishitsuka Tatsuya Ogawa Dennis Roop The KEAP1/NRF2 Signaling Pathway in Keratinization Antioxidants gene expression regulation environmental response squamous epithelium KEAP1/NRF2 signaling keratinization thiol |
| title | The KEAP1/NRF2 Signaling Pathway in Keratinization |
| title_full | The KEAP1/NRF2 Signaling Pathway in Keratinization |
| title_fullStr | The KEAP1/NRF2 Signaling Pathway in Keratinization |
| title_full_unstemmed | The KEAP1/NRF2 Signaling Pathway in Keratinization |
| title_short | The KEAP1/NRF2 Signaling Pathway in Keratinization |
| title_sort | keap1 nrf2 signaling pathway in keratinization |
| topic | gene expression regulation environmental response squamous epithelium KEAP1/NRF2 signaling keratinization thiol |
| url | https://www.mdpi.com/2076-3921/9/8/751 |
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