ArticleMolecular biology of the cell2007
LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.
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Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it, 321 citations in OpenAlex.
- Outcomes of Systemic Treatment in Children and Adults With Netherton Syndrome: A Systematic Review.Frontiers in immunology · 2022Pooled it
- An Investigational Mechanism-Informed Therapy for Netherton Syndrome: Introduction to QRX003 and A Pediatric Compassionate-Use Case Report.Dermatology and therapy · 2026Review
- Integrative Approaches to Atopic Dermatitis: Exploring Biomarkers, Current Therapies, and the Potential Role of Osteopathic Manipulative Medicine.International journal of molecular sciences · 2026Review
- Occupational Contact Dermatitis in the Post-COVID Era: From Barrier Dysfunction and Microbiome Dysbiosis to Prevention and Precision Management.Journal of clinical medicine · 2026Review
- SPINK2 in hematopoiesis and cancer: Biology and clinical implications.Cell death discovery · 2026Review
- IL-13 and calpain-14 suppress the expression of SPINK7 by regulating OVOL1 in eosinophilic esophagitis.JCI insight · 2026Article
- Dysregulated proteolytic cascades in Netherton syndrome: from molecular pathology to preclinical drug testing.The Journal of pathology · 2026Review
- From acidification to multi-targeted cellular modulation: dual impact of hydroxy acids on the skin microbiota and the epidermal barrier.Frontiers in cellular and infection microbiology · 2026Review
- Drug Discovery Strategies for Kallikrein-Related Peptidases.International journal of molecular sciences · 2025Review
- LEKTI-Grafted Sunflower Trypsin Inhibitor: A Potential Therapeutic for Skin Diseases.Journal of medicinal chemistry · 2025Article
- Insights into platypus crural gland transcriptomics - venom and beyond.BMC genomics · 2025Article
- The SPINK Protein Family in Cancer: Emerging Roles in Tumor Progression, Therapeutic Resistance, and Precision Oncology.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Secukinumab as a Novel Treatment for Chronic Netherton Syndrome in a Young Adult.The American journal of case reports · 2025Article
- Kallikrein-8 mediates furin-independent Activin-A precursor processing to stimulate tumor growth in melanoma.Nature communications · 2025Article
- Developing a Core Outcome Set for Netherton Syndrome: An International Multi-Stakeholder e-Delphi Consensus Study.Dermatology (Basel, Switzerland) · 2025Article
- Revisiting the human umbilical cord epithelium. An atypical epithelial sheath with distinctive features.Cell and tissue research · 2024Article
- Polysaccharide, Conjugate, and mRNA-based Vaccines are Immunogenic in Patients with Netherton Syndrome.Journal of clinical immunology · 2024Article
- Interleukin-36 Is Highly Expressed in Skin Biopsies from Two Patients with Netherton Syndrome.Dermatopathology (Basel, Switzerland) · 2024Article
- Recombinant scFv-Fc Anti-kallikrein 7 Antibody-Loaded Thermosensitive Hydrogels Against Skin Desquamation Disorders.ACS applied bio materials · 2024Article
- Overlap of eosinophilic esophagitis with inborn errors of immunity and immune dysregulation.The Journal of allergy and clinical immunology · 2024Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
LEKTI is a 15-domain serine proteinase inhibitor whose defective expression underlies the severe autosomal recessive ichthyosiform skin disease, Netherton syndrome. Here, we show that LEKTI is produced as a precursor rapidly cleaved by furin, generating a variety of single or multidomain LEKTI fragments secreted in cultured keratinocytes and in the epidermis. The identity of these biological fragments (D1, D5, D6, D8-D11, and D9-D15) was inferred from biochemical analysis, using a panel of LEKTI antibodies. The functional inhibitory capacity of each fragment was tested on a panel of serine proteases. All LEKTI fragments, except D1, showed specific and differential inhibition of human kallikreins 5, 7, and 14. The strongest inhibition was observed with D8-D11, toward KLK5. Kinetics analysis revealed that this interaction is rapid and irreversible, reflecting an extremely tight binding complex. We demonstrated that pH variations govern this interaction, leading to the release of active KLK5 from the complex at acidic pH. These results identify KLK5, a key actor of the desquamation process, as the major target of LEKTI. They disclose a new mechanism of skin homeostasis by which the epidermal pH gradient allows precisely regulated KLK5 activity and corneodesmosomal cleavage in the most superficial layers of the stratum corneum.
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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.