ArticleThe Journal of investigative dermatology2012
Urea uptake enhances barrier function and antimicrobial defense in humans by regulating epidermal gene expression.
Article in The Journal of investigative dermatology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 173 citations in OpenAlex.
- Hygiene and emollient interventions for maintaining skin integrity in older people in hospital and residential care settings.The Cochrane database of systematic reviews · 2020Pooled it
- Different types of emollient cream exhibit diverse physiological effects on the skin barrier in adults with atopic dermatitis.Clinical and experimental dermatology · 2022Trial
- Trial
- Development and internal-external validation of a machine learning-based risk prediction model for multidrug resistance in mechanically ventilated ICU patients with chronic obstructive pulmonary disease.Frontiers in medicine · 2026Article
- Topical regimens for the management of uremic pruritus.Frontiers in medicine · 2026Review
- Review
- TEAL-Seq: targeted expression analysis sequencing.mSphere · 2025Article
- Urea Transport Mediated by Membrane Proteins of Non-urea-Transporters.Sub-cellular biochemistry · 2025Review
- Overview of popular cosmeceuticals in dermatology.Skin health and disease · 2024Review
- Effects of a leave-on product on the strength of the dermoepidermal junction: An exploratory, intraindividual, randomized controlled trial in older adults with dry skin.Health science reports · 2024Article
- Targeting Skin Barrier Function in Atopic Dermatitis.The journal of allergy and clinical immunology. In practice · 2023Article
- The foot in diabetes - a reminder of an ever-present risk.Clinical medicine (London, England) · 2023Review
- Aquaporins in Skin.Advances in experimental medicine and biology · 2023Article
- 0.5-5% Supramolecular Salicylic Acid Hydrogel is Safe for Long-Term Topical Application and Improves the Expression of Genes Related to Skin Barrier Homeostasis in Mice Models.Drug design, development and therapy · 2023Article
- The Effects of Mucopolysaccharide Polysulfate on Steroid-Induced Tight Junction Barrier Dysfunction in Human Epidermal Keratinocytes and a 3D Skin Model.Skin pharmacology and physiology · 2023Article
- Transport Characteristics of Aquaporins.Advances in experimental medicine and biology · 2023Article
- Skin Care Product Rich in Antioxidants and Anti-Inflammatory Natural Compounds Reduces Itching and Inflammation in the Skin of Atopic Dermatitis Patients.Antioxidants (Basel, Switzerland) · 2022Article
- The Use of Urea Cream for Hand Eczema and Urea Foam for Seborrheic Dermatitis and Psoriasiform Dermatoses of the Scalp.Clinical, cosmetic and investigational dermatology · 2022Article
- Urea in Dermatology: A Review of its Emollient, Moisturizing, Keratolytic, Skin Barrier Enhancing and Antimicrobial Properties.Dermatology and therapy · 2021Review
- Beyond CaPflugers Archiv : European journal of physiology · 2021Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Urea is an endogenous metabolite, known to enhance stratum corneum hydration. Yet, topical urea anecdotally also improves permeability barrier function, and it appears to exhibit antimicrobial activity. Hence, we hypothesized that urea is not merely a passive metabolite, but a small-molecule regulator of epidermal structure and function. In 21 human volunteers, topical urea improved barrier function in parallel with enhanced antimicrobial peptide (AMP; LL-37 and β-defensin-2) expression. Urea stimulates the expression of, and is transported into, keratinocytes by two urea transporters (UTs), UT-A1 and UT-A2, and by aquaporins 3, 7, and 9. Inhibitors of these UTs block the downstream biological effects of urea, which include increased mRNA and protein levels of (i) transglutaminase-1, involucrin, loricrin, and filaggrin, (ii) epidermal lipid synthetic enzymes, and (iii) cathelicidin/LL-37 and β-defensin-2. Finally, we explored the potential clinical utility of urea, showing that topical urea applications normalized both barrier function and AMP expression in a murine model of atopic dermatitis. Together, these results show that urea is a small-molecule regulator of epidermal permeability barrier function and AMP expression after transporter uptake, followed by gene regulatory activity in normal epidermis, with potential therapeutic applications in diseased skin.
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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.