Evidence map›Paper›PMID 25602157›Full record

ArticleThe Journal of investigative dermatology2015

Genetic and pharmacological analysis identifies a physiological role for the AHR in epidermal differentiation.

Ellen H van den Bogaard, Michael A Podolsky, Jos P Smits, Xiao Cui, Christian John, Krishne Gowda, Dhimant Desai, Shantu G Amin, Joost Schalkwijk, Gary H Perdew and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of investigative dermatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.

  1. Pooled it
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  5. Article
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  7. Article
  8. The Aryl Hydrocarbon Receptor (AHR): Peacekeeper of the Skin.International journal of molecular sciences · 2025
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 2 countries.

Ellen H van den BogaardDepartment of Dermatology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
Michael A PodolskyDepartment of Veterinary and Biomedical Sciences, Pennsylvania State University, Carlisle, PA, USA.
Jos P SmitsDepartment of Dermatology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
Xiao CuiDepartment of Veterinary and Biomedical Sciences, Pennsylvania State University, Carlisle, PA, USA.
Christian JohnDepartment of Veterinary and Biomedical Sciences, Pennsylvania State University, Carlisle, PA, USA.
Krishne GowdaDepartment of Pharmacology, Pennsylvania State College of Medicine, Hershey, PA, USA.
Dhimant DesaiDepartment of Pharmacology, Pennsylvania State College of Medicine, Hershey, PA, USA.
Shantu G AminDepartment of Pharmacology, Pennsylvania State College of Medicine, Hershey, PA, USA.
Joost SchalkwijkDepartment of Dermatology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
Gary H PerdewDepartment of Veterinary and Biomedical Sciences, Pennsylvania State University, Carlisle, PA, USA.
Adam B GlickDepartment of Veterinary and Biomedical Sciences, Pennsylvania State University, Carlisle, PA, USA. Electronic address: abg11@psu.edu.
Pennsylvania State University · USPenn State Milton S. Hershey Medical Center · USRadboud University Nijmegen · NL

Funding

REGULATION OF THE AH RECEPTORR01ES004869 · NIEHS · PURDUE UNIVERSITY WEST LAFAYETTE · PI PERDEW, GARY H. · 1994 to 2017
$5.3M
Selective Ah Receptor Ligands Repress Acute-Phase ResponseR01ES019964 · NIEHS · PENNSYLVANIA STATE UNIVERSITY, THE · PI PERDEW, GARY H. · 2012 to 2016
$2.0M
Suppression of Cancer Inflammation with AHR ModulatorsR21ES020922 · NIEHS · PENNSYLVANIA STATE UNIVERSITY, THE · PI GLICK, ADAM B · 2012 to 2013
$390k
NIEHS NIH HHS 1R21ES020922NIEHS NIH HHS R01 ES004869NIEHS NIH HHS R01ES004869NIEHS NIH HHS R01 ES019964NIEHS NIH HHS R01ES19964NIEHS NIH HHS R21 ES020922
6 · The paper itself

Abstract

Stimulation of the aryl hydrocarbon receptor (AHR) by xenobiotics is known to affect epidermal differentiation and skin barrier formation. The physiological role of endogenous AHR signaling in keratinocyte differentiation is not known. We used murine and human skin models to address the hypothesis that AHR activation is required for normal keratinocyte differentiation. Using transcriptome analysis of Ahr(-/-) and Ahr(+/+) murine keratinocytes, we found significant enrichment of differentially expressed genes linked to epidermal differentiation. Primary Ahr(-/-) keratinocytes showed a significant reduction in terminal differentiation gene and protein expression, similar to Ahr(+/+) keratinocytes treated with AHR antagonists GNF351 and CH223191, or the selective AHR modulator (SAhRM) SGA360. In vitro keratinocyte differentiation led to increased AHR levels and subsequent nuclear translocation, followed by induced CYP1A1 gene expression. Monolayer cultured primary human keratinocytes treated with AHR antagonists also showed an impaired terminal differentiation program. Inactivation of AHR activity during human skin equivalent development severely impaired epidermal stratification, terminal differentiation protein expression, and stratum corneum formation. As disturbed epidermal differentiation is a main feature of many skin diseases, pharmacological agents targeting AHR signaling or future identification of endogenous keratinocyte-derived AHR ligands should be considered as potential new drugs in dermatology.

Indexed as

Epidermal CellsAllyl CompoundsAnimalsAzo CompoundsCell AdhesionCell DifferentiationCells, CulturedEpidermisHumansIndazolesIndolesKeratinocytesMiceMice, KnockoutModels, AnimalPurines2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amideAllyl CompoundsAzo CompoundsIndazolesIndolesN-(2-(3H-indol-3-yl)ethyl)-9-isopropyl-2-(5-methyl-3-pyridyl)purin-6-aminePurinesPyrazolesReceptors, Aryl HydrocarbonSGA 360

Identifiers

PMID25602157
PMCPMC4402116
OpenAlexW2060505238

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.