ArticleThe Journal of investigative dermatology2018
Epidermal Overexpression of Xenobiotic Receptor PXR Impairs the Epidermal Barrier and Triggers Th2 Immune Response.
Article in The Journal of investigative dermatology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- PPARα deficiency causes skin dysbiosis and triggers innate immunity in keratinocytes.Cell death & disease · 2026Article
- Pregnane X receptor reduces particulate matter-induced type 17 inflammation in atopic dermatitis.Frontiers in immunology · 2024Article
- The Burden of Air Pollution on Skin Health: a Brief Report and Call to Action.Dermatology and therapy · 2024Article
- Review
- Article
- Role of nuclear receptor PXR in immune cells and inflammatory diseases.Frontiers in immunology · 2022Review
- Metabolomic analysis of vascular cognitive impairment due to hepatocellular carcinoma.Frontiers in neurology · 2022Article
- Peroxisomal Fatty Acid Oxidation and Glycolysis Are Triggered in Mouse Models of Lesional Atopic Dermatitis.JID innovations : skin science from molecules to population health · 2021Article
- Climate change and pediatric skin health.International journal of women's dermatology · 2021Review
- Xenobiotic Receptors and Their Mates in Atopic Dermatitis.International journal of molecular sciences · 2019Review
- Evolutionary Plasticity in Detoxification Gene Modules: The Preservation and Loss of the Pregnane X Receptor in Chondrichthyes Lineages.International journal of molecular sciences · 2019Article
- Filaggrin null mutations are associated with altered circulating Tregs in atopic dermatitis.Journal of cellular and molecular medicine · 2019Article
- IRRITANT AND ALLERGIC CONTACT DERMATITIS - SKIN LESION CHARACTERISTICS.Acta clinica Croatica · 2018Review
- The Roles of Xenobiotic Receptors: Beyond Chemical Disposition.Drug metabolism and disposition: the biological fate of chemicals · 2018Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The skin is in daily contact with environmental pollutants, but the long-term effects of such exposure remain underinvestigated. Many of these toxins bind and activate the pregnane X receptor (PXR), a ligand-activated transcription factor that regulates genes central to xenobiotic metabolism. The objective of this work was to investigate the effect of constitutive activation of PXR in the basal layer of the skin to mimic repeated skin exposure to noxious molecules. We designed a transgenic mouse model that overexpresses the human PXR gene linked to the herpes simplex VP16 domain under the control of the keratin 14 promoter. We show that transgenic mice display increased transepidermal water loss and elevated skin pH, abnormal stratum corneum lipids, focal epidermal hyperplasia, activated keratinocytes expressing more thymic stromal lymphopoietin, a T helper type 2/T helper type 17 skin immune response, and increased serum IgE. Furthermore, the cutaneous barrier dysfunction precedes development of the T helper type 2/T helper type 17 inflammation in transgenic mice, thereby mirroring the time course of atopic dermatitis development in humans. Moreover, further experiments suggest increased PXR signaling in the skin of patients with atopic dermatitis when compared with healthy skin. Thus, PXR activation by environmental pollutants may compromise epidermal barrier function and favor an immune response resembling atopic dermatitis.
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Registered trials
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.