ArticleThe Journal of allergy and clinical immunology2017
Proteomic analysis of filaggrin deficiency identifies molecular signatures characteristic of atopic eczema.
Article in The Journal of allergy and clinical immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled 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.
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
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation.Nature communications · 2023Pooled it
- Microbiome dysbiosis and therapeutic restoration in atopic dermatitis.Frontiers in cellular and infection microbiology · 2026Review
- Transcriptome-wide analyses delineate the genetic architecture of expression variation in atopic dermatitis.HGG advances · 2025Article
- Article
- Development of pathological skin models: from conventional techniques to 3D bioprinting.Frontiers in bioengineering and biotechnology · 2025Review
- Unraveling genetic threads: Identifying novel therapeutic targets for allergic rhinitis through Mendelian randomization.The World Allergy Organization journal · 2024Article
- Keratinocyte-derived small extracellular vesicles supply antigens for CD1a-resticted T cells and promote their type 2 bias in the context of filaggrin insufficiency.Frontiers in immunology · 2024Article
- Immunomodulatory potential of primary cilia in the skin.Frontiers in immunology · 2024Review
- Advanced In Vitro Three-Dimensional Skin Models of Atopic Dermatitis.Tissue engineering and regenerative medicine · 2023Review
- Epicutaneous Sensitization and Food Allergy: Preventive Strategies Targeting Skin Barrier Repair-Facts and Challenges.Nutrients · 2023Review
- Cutaneous immune-related adverse events to immune checkpoint inhibitors: from underlying immunological mechanisms to multi-omics prediction.Frontiers in immunology · 2023Review
- Article
- The immunological and structural epidermal barrier dysfunction and skin microbiome in atopic dermatitis-an update.Frontiers in molecular biosciences · 2023Review
- Identification of Cofilin-1 as a novel biomarker of atopic dermatitis using iTRAQ quantitative proteomics.Journal of clinical laboratory analysis · 2022Article
- An Inflamed and Infected Reconstructed Human Epidermis to Study Atopic Dermatitis and Skin Care Ingredients.International journal of molecular sciences · 2022Article
- Review
- Revisiting the Roles of Filaggrin in Atopic Dermatitis.International journal of molecular sciences · 2022Review
- Epithelial barrier hypothesis: Effect of the external exposome on the microbiome and epithelial barriers in allergic disease.Allergy · 2022Review
- Immunomodulatory Role ofPathogens (Basel, Switzerland) · 2022Review
- The Inflammatory Response in Human Keratinocytes Exposed to Cinnamaldehyde Is Regulated by Nrf2.Antioxidants (Basel, Switzerland) · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAtopic eczema (AE) is characterized by skin barrier and immune dysfunction. Null mutations in filaggrin (FLG), a key epidermal barrier protein, strongly predispose to AE; however, the precise role of FLG deficiency in AE pathogenesis remains incompletely understood.
objectivesWe sought to identify global proteomic changes downstream of FLG deficiency in human epidermal living skin-equivalent (LSE) models and validate findings in skin of patients with AE.
methodsDifferentially expressed proteins from paired control (nontargeting control short hairpin RNA [shNT]) and FLG knockdown (FLG knockdown short hairpin RNA [shFLG]) LSEs were identified by means of proteomic analysis (liquid chromatography-mass spectrometry) and Ingenuity Pathway Analysis. Expression of key targets was validated in independent LSE samples (quantitative RT-PCR and Western blotting) and in normal and AE skin biopsy specimens (immunofluorescence).
resultsProteomic analysis identified 17 (P ≤ .05) differentially expressed proteins after FLG knockdown, including kallikrein-7 (KLK7; 2.2-fold), cyclophilin A (PPIA; 0.9-fold), and cofilin-1 (CFL1, 1.3-fold). Differential protein expression was confirmed in shNT/shFLG LSEs; however, only KLK7 was transcriptionally dysregulated. Molecular pathways overrepresented after FLG knockdown included inflammation, protease activity, cell structure, and stress. Furthermore, KLK7 (1.8-fold) and PPIA (0.65-fold) proteins were differentially expressed in lesional biopsy specimens from patients with AE relative to normal skin.
conclusionsFor the first time, we show that loss of FLG in the absence of inflammation is sufficient to alter the expression level of proteins relevant to the pathogenesis of AE. These include proteins regulating inflammatory, proteolytic, and cytoskeletal functions. We identify PPIA as a novel protein with levels that are decreased in clinically active AE skin and show that the characteristic upregulation of KLK7 expression in patients with AE occurs downstream of FLG loss. Importantly, we highlight disconnect between the epidermal proteome and transcriptome, emphasizing the utility of global proteomic studies.
Indexed as
Identifiers
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.