ArticleThe Journal of experimental medicine2012
Epidermal ADAM17 maintains the skin barrier by regulating EGFR ligand-dependent terminal keratinocyte differentiation.
Article in The Journal of experimental medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 108 papers.
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.
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.
Who cites it
108 citing papers in PubMed, 184 citations in OpenAlex.
- ADAM17 and its proteolytic targets in disease pathogenesis.The FEBS journal · 2026Review
- Structural basis for ADAM17 activation by the iRhom1 pseudoprotease.Cell reports · 2026Article
- Anaerobe-Driven Inflammation and Epithelial Barrier Disruption in Genital HIV Acquisition.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Review
- The dynamics of mutational selection in cutaneous squamous carcinogenesis.Communications biology · 2026Article
- Chinese botanical drugs for mitigating epidermal growth factor receptor-targeted therapy-associated cutaneous toxicity: immune mechanisms and translational pathways.Frontiers in pharmacology · 2026Review
- From basic biology to engineered therapies: the keratinocyte stem cell playbook.Frontiers in medical technology · 2026Review
- Transforming growth factor alpha promotes bullous pemphigoid pathogenesis by disrupting cell adhesion and inducing inflammation.Cellular and molecular life sciences : CMLS · 2025Article
- Catalytic Site Inhibitors of Group 1 Allergens Prevent Toll-like Receptor (TLR)4- and TLR1/2-Dependent Innate Responses in Keratinocytes and Airway Epithelial Cells Exposed to House Dust Mite Allergenic Extract.ACS pharmacology & translational science · 2025Article
- Structural insights into the activation and inhibition of the ADAM17-iRhom2 complex.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Conversation between skin microbiota and the host: from early life to adulthood.Experimental & molecular medicine · 2025Review
- EGF receptor in organ development, tissue homeostasis and regeneration.Journal of biomedical science · 2025Review
- zDHHC-Mediated S-Palmitoylation in Skin Health and Its Targeting as a Treatment Perspective.International journal of molecular sciences · 2025Review
- The role of the interleukin family in liver fibrosis.Frontiers in immunology · 2025Review
- Natural killer cells in skin: a unique opportunity to better characterize the many facets of an overlooked secondary lymphoid organ.Frontiers in immunology · 2025Review
- Focus on Interferon Signature in Cutaneous Lupus Erythematosus: Novel Therapies From Better Understanding of the Pathogenesis.Journal of immunology research · 2025Review
- JAK-STAT1 as therapeutic target for EGFR deficiency-associated inflammation and scarring alopecia.EMBO molecular medicine · 2024Article
- Receptor Tyrosine Kinase EPHA2 Drives Epidermal Differentiation through Regulation of EGFR Signaling.The Journal of investigative dermatology · 2024Article
- [Ultraviolet radiation in the pathogenesis of lupus erythematosus].Dermatologie (Heidelberg, Germany) · 2024Review
- Article
48 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
ADAM17 (a disintegrin and metalloproteinase 17) is ubiquitously expressed and cleaves membrane proteins, such as epidermal growth factor receptor (EGFR) ligands, l-selectin, and TNF, from the cell surface, thus regulating responses to tissue injury and inflammation. However, little is currently known about its role in skin homeostasis. We show that mice lacking ADAM17 in keratinocytes (A17(ΔKC)) have a normal epidermal barrier and skin architecture at birth but develop pronounced defects in epidermal barrier integrity soon after birth and develop chronic dermatitis as adults. The dysregulated expression of epidermal differentiation proteins becomes evident 2 d after birth, followed by reduced transglutaminase (TGM) activity, transepidermal water loss, up-regulation of the proinflammatory cytokine IL-36α, and inflammatory immune cell infiltration. Activation of the EGFR was strongly reduced in A17(ΔKC) skin, and topical treatment of A17(ΔKC) mice with recombinant TGF-α significantly improved TGM activity and decreased skin inflammation. Finally, we show that mice lacking the EGFR in keratinocytes (Egfr(ΔKC)) closely resembled A17(ΔKC) mice. Collectively, these results identify a previously unappreciated critical role of the ADAM17-EGFR signaling axis in maintaining the homeostasis of the postnatal epidermal barrier and suggest that this pathway could represent a good target for treatment of epidermal barrier defects.
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What OpenQuestion holds
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.