ArticleThe Journal of clinical investigation2014
A GRHL3-regulated repair pathway suppresses immune-mediated epidermal hyperplasia.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Meta-Analysis ofGenes · 2019Pooled it
- Review
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- Multifocal Epithelial Hyperplasia: Persistence in Adulthood and Treatment-A Case Report.Case reports in dentistry · 2026Article
- Transcriptional and epigenetic mechanisms governing epidermal stem cell regulation.Frontiers in cell and developmental biology · 2026Review
- Long-term cytokine exposure remodels the methylome and transcriptome of recessive dystrophic epidermolysis bullosa keratinocytes - a bioinformatic analysis.Frontiers in cell and developmental biology · 2026Article
- Loss of the epithelial transcription factor grhl3 leads to variably penetrant developmental phenotypes in zebrafish.Developmental dynamics : an official publication of the American Association of Anatomists · 2025Article
- Multimodal Function of Mesenchymal Stem Cells in Psoriasis Treatment.Biomolecules · 2025Review
- Expression network analysis of bovine skin infested with Rhipicephalus australis identifies pro-inflammatory genes contributing to tick susceptibility.Scientific reports · 2024Article
- Functions of the RIP kinase family members in the skin.Cellular and molecular life sciences : CMLS · 2023Review
- Epidermis-Intrinsic Transcription Factor Ovol1 Coordinately Regulates Barrier Maintenance and Neutrophil Accumulation in Psoriasis-Like Inflammation.The Journal of investigative dermatology · 2022Article
- Advances in the pathogenesis of psoriasis: from keratinocyte perspective.Cell death & disease · 2022Review
- Fanning the Flames: IRAK2 Signaling in Differentiated Epithelium Potentiates Skin Inflammation.The Journal of investigative dermatology · 2021Article
- IRAK2 Has a Critical Role in Promoting Feed-Forward Amplification of Epidermal Inflammatory Responses.The Journal of investigative dermatology · 2021Article
- GRHL3 activates FSCN1 to relax cell-cell adhesions between migrating keratinocytes during wound reepithelialization.JCI insight · 2021Article
- Grhl3 promotes retention of epidermal cells under endocytic stress to maintain epidermal architecture in zebrafish.PLoS genetics · 2021Article
- Chromatin Looping Links Target Genes with Genetic Risk Loci for Dermatological Traits.The Journal of investigative dermatology · 2021Article
- Transcriptional and signalling regulation of skin epithelial stem cells in homeostasis, wounds and cancer.Experimental dermatology · 2021Review
- Desmosomes as Signaling Hubs in the Regulation of Cell Behavior.Frontiers in cell and developmental biology · 2021Review
- GRHL3 Promotes Tumor Growth and Metastasis via the MEK Pathway in Colorectal Cancer.Analytical cellular pathology (Amsterdam) · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Dermal infiltration of T cells is an important step in the onset and progression of immune-mediated skin diseases such as psoriasis; however, it is not known whether epidermal factors play a primary role in the development of these diseases. Here, we determined that the prodifferentiation transcription factor grainyhead-like 3 (GRHL3), which is essential during epidermal development, is dispensable for adult skin homeostasis, but required for barrier repair after adult epidermal injury. Consistent with activation of a GRHL3-regulated repair pathway in psoriasis, we found that GRHL3 is upregulated in lesional skin and binds known epidermal differentiation gene targets. Using an imiquimod-induced model of immune-mediated epidermal hyperplasia, we found that mice lacking GRHL3 have an exacerbated epidermal damage response, greater sensitivity to disease induction, delayed resolution of epidermal lesions, and resistance to anti-IL-22 therapy compared with WT animals. ChIP-Seq and gene expression profiling of murine skin revealed that while GRHL3 regulates differentiation pathways both during development and during repair from immune-mediated damage, it targets distinct sets of genes in the 2 processes. In particular, GRHL3 suppressed a number of alarmin and other proinflammatory genes after immune injury. This study identifies a GRHL3-regulated epidermal barrier repair pathway that suppresses disease initiation and helps resolve existing lesions in immune-mediated epidermal hyperplasia.
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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.