ArticlePLoS genetics2017
KLK5 and KLK7 Ablation Fully Rescues Lethality of Netherton Syndrome-Like Phenotype.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 92 citations in OpenAlex.
- An Investigational Mechanism-Informed Therapy for Netherton Syndrome: Introduction to QRX003 and A Pediatric Compassionate-Use Case Report.Dermatology and therapy · 2026Review
- The potential effects, mechanisms and translational perspectives of natural products in the treatment of atopic dermatitis.Chinese medicine · 2026Review
- Diosmetin, an active ingredient of Schizonepeta tenuifolia, alleviates acne by regulating inflammation and oxidative stress.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Dysregulated proteolytic cascades in Netherton syndrome: from molecular pathology to preclinical drug testing.The Journal of pathology · 2026Review
- Generation and characterization of a Cre-inducible MAP3K1 gain-of-function model.Disease models & mechanisms · 2026Article
- From Adipose Tissue to Endothelial Cells-Pleiotropic Role of Vaspin in Pathogenesis of Metabolic and Cardiovascular Diseases.Biomedicines · 2025Review
- Deletion of the Epidermal ProteaseInternational journal of molecular sciences · 2025Article
- Atopic Dermatitis: The Relationship Between Immune Mediators and Skin Lipid Barrier.Clinical reviews in allergy & immunology · 2025Review
- The antiprotease Spink7 promotes inflammation resolution by modulating multiple proteases activities during wound healing.Clinical and translational medicine · 2025Article
- Recombinant scFv-Fc Anti-kallikrein 7 Antibody-Loaded Thermosensitive Hydrogels Against Skin Desquamation Disorders.ACS applied bio materials · 2024Article
- Comparative analyses of Netherton syndrome patients and Spink5 conditional knock-out mice uncover disease-relevant pathways.Communications biology · 2024Article
- Retrospective pharmacogenetic study of psoriasis highlights the role of KLK7 in tumour necrosis factor signalling.The British journal of dermatology · 2023Article
- The Slough of Cicadidae Periostracum Ameliorated Lichenification by Inhibiting Interleukin (IL)-22/Janus Kinase (JAK) 1/Signal Transducer and Activator of Transcription (STAT) 3 Pathway in Atopic Dermatitis.Food science of animal resources · 2023Article
- Overcoming Soluble Target Interference in Measurement of Total Bispecific Therapeutic Antibody Concentrations.The AAPS journal · 2023Article
- Proteomic profiling of sweat in patients with cystic fibrosis provides new insights into epidermal homoeostasis.Skin health and disease · 2023Article
- Novel specific activity-based probes validate KLK proteases as druggable targets.Cancer biology & therapy · 2022Article
- Resolution of Eczema with Multivalent Peptides.JID innovations : skin science from molecules to population health · 2022Article
- New developments in the molecular treatment of ichthyosis: review of the literature.Orphanet journal of rare diseases · 2022Review
- Activity-Based Probes for Proteases Pave the Way to Theranostic Applications.Pharmaceutics · 2022Review
- Cocktails of KLK5 Protease Inhibitors and Anti-TNFα Therapeutics: an Effective Treatment for Netherton Syndrome.Journal of clinical immunology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Netherton syndrome (NS) is a severe skin disease caused by the loss of protease inhibitor LEKTI, which leads to the dysregulation of epidermal proteases and severe skin-barrier defects. KLK5 was proposed as a major protease in NS pathology, however its inactivation is not sufficient to rescue the lethal phenotype of LEKTI-deficient mice. In this study, we further elucidated the in vivo roles of the epidermal proteases in NS using a set of mouse models individually or simultaneously deficient for KLK5 and KLK7 on the genetic background of a novel NS-mouse model. We show that although the ablation of KLK5 or KLK7 is not sufficient to rescue the lethal effect of LEKTI-deficiency simultaneous deficiency of both KLKs completely rescues the epidermal barrier and the postnatal lethality allowing mice to reach adulthood with fully functional skin and normal hair growth. We report that not only KLK5 but also KLK7 plays an important role in the inflammation and defective differentiation in NS and KLK7 activity is not solely dependent on activation by KLK5. Altogether, these findings show that unregulated activities of KLK5 and KLK7 are responsible for NS development and both proteases should become targets for NS therapy.
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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.