ArticleEMBO molecular medicine2014
Activation of Nrf2 in keratinocytes causes chloracne (MADISH)-like skin disease in mice.
Article in EMBO molecular medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 95 citations in OpenAlex.
- Comparative 28-day mouse study of topically applied aryl hydrocarbon receptor ligands: microbiota-derived indoles, therapeutic tapinarof, pollutants 2,3,7,8-tetrachlorodibenzo-p-dioxin and diesel exhaust particles.Chemico-biological interactions · 2026Article
- AHR: The Overlooked Mediator in SkincareBridging Environmental Sensing and Skin Physiology.Environment & health (Washington, D.C.) · 2026Review
- Dysregulated proteolytic cascades in Netherton syndrome: from molecular pathology to preclinical drug testing.The Journal of pathology · 2026Review
- Various Cellular Components and Its Signaling Cascades Through the Involvement of Signaling Messengers in Keratinocyte Differentiation.Antioxidants (Basel, Switzerland) · 2025Review
- New insights into coordinated regulation of AHR promoter transcription; molecular mechanisms and therapeutic targets.International journal of biological sciences · 2025Review
- Dose-dependent effects of Nrf2 on the epidermis in chronic skin inflammation.Disease models & mechanisms · 2025Article
- Hair follicles modulate skin barrier function.Cell reports · 2024Article
- Hair follicles modulate skin barrier function.bioRxiv : the preprint server for biology · 2024Article
- Conditional Knockout of N-WASP Enhanced the Formation of Keratinizing Squamous Cell Carcinoma Induced by KRasCancers · 2023Article
- Exploring cell competition for the prevention and therapy of esophageal squamous cell carcinoma.Biochemical pharmacology · 2023Review
- NRF2 Controls the Competitive Fitness of Squamous Epithelial Cells in the Mouse Esophagus.Cellular and molecular gastroenterology and hepatology · 2023Article
- Review
- NRF2 in dermatological disorders: Pharmacological activation for protection against cutaneous photodamage and photodermatosis.Free radical biology & medicine · 2022Review
- The Role of KEAP1-NRF2 System in Atopic Dermatitis and Psoriasis.Antioxidants (Basel, Switzerland) · 2022Review
- AHR and NRF2 in Skin Homeostasis and Atopic Dermatitis.Antioxidants (Basel, Switzerland) · 2022Review
- Loricrin and NRF2 Coordinate Cornification.JID innovations : skin science from molecules to population health · 2022Article
- Alopecia in Multiple Sclerosis Patients Treated with Disease Modifying Therapies.Journal of central nervous system disease · 2022Article
- The Epidermis: Redox Governor of Health and Diseases.Antioxidants (Basel, Switzerland) · 2021Review
- Upregulation of CCL7, CCL20, CXCL2, IL-1β, IL-6 and MMP-9 in Skin Samples of PCB Exposed Individuals-A Preliminary Study.International journal of environmental research and public health · 2021Article
- Regulatory Role of Nrf2 Signaling Pathway in Wound Healing Process.Molecules (Basel, Switzerland) · 2021Review
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Authors and funding
18 authors at 10 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transcription factor Nrf2 is a key regulator of the cellular stress response, and pharmacological Nrf2 activation is a promising strategy for skin protection and cancer prevention. We show here that prolonged Nrf2 activation in keratinocytes causes sebaceous gland enlargement and seborrhea in mice due to upregulation of the growth factor epigen, which we identified as a novel Nrf2 target. This was accompanied by thickening and hyperkeratosis of hair follicle infundibula. These abnormalities caused dilatation of infundibula, hair loss, and cyst development upon aging. Upregulation of epigen, secretory leukocyte peptidase inhibitor (Slpi), and small proline-rich protein 2d (Sprr2d) in hair follicles was identified as the likely cause of infundibular acanthosis, hyperkeratosis, and cyst formation. These alterations were highly reminiscent to the phenotype of chloracne/"metabolizing acquired dioxin-induced skin hamartomas" (MADISH) patients. Indeed, SLPI, SPRR2, and epigen were strongly expressed in cysts of MADISH patients and upregulated by dioxin in human keratinocytes in an NRF2-dependent manner. These results identify novel Nrf2 activities in the pilosebaceous unit and point to a role of NRF2 in MADISH pathogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.