ArticleThe Journal of clinical investigation2020
KLK6 expression in skin induces PAR1-mediated psoriasiform dermatitis and inflammatory joint disease.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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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
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Impact of Biologic Therapies on the Risk of Progression from Psoriasis to Psoriatic Arthritis: A Systematic Review and Meta-Analysis of Cohort Studies.American journal of clinical dermatology · 2026Pooled it
- Divergent Paths: A Comprehensive Review of Mechanisms and Clinical Implications in Atopic Dermatitis and Psoriasis.Allergy · 2026Review
- Dysregulated proteolytic cascades in Netherton syndrome: from molecular pathology to preclinical drug testing.The Journal of pathology · 2026Review
- Unrestrained MyD88 Signaling in A20-Deficient Keratinocytes Triggers T-Cell-Dependent Psoriatic Arthritis-Like Disease.The Journal of investigative dermatology · 2025Article
- Human tissue kallikrein 14 induces the expression of IL-6, IL-8, and CXCL1 in skin fibroblasts through protease-activated receptor 1 signaling.The FEBS journal · 2025Article
- G-CSF Mediates Increased Renal Neutrophils and Kidney Damage in a Psoriasis Mouse Model.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Uncovering a fibroblast differentiation-based keloid classification by integration of single-cell and bulk RNA sequencing.Communications biology · 2025Article
- Sex Bias in Autoimmunity: New Findings and New Opportunities.JID innovations : skin science from molecules to population health · 2025Review
- CXCL10 secreted by SPRY1-deficient epidermal keratinocytes fuels joint inflammation in psoriatic arthritis via CD14 signaling.The Journal of clinical investigation · 2025Article
- Psoriasiform Dermatitis: From Pathogenesis to New Therapeutic Opportunities.Life (Basel, Switzerland) · 2025Review
- The Inflammatory Link of Rheumatoid Arthritis and Thrombosis: Pathogenic Molecular Circuits and Treatment Approaches.Current issues in molecular biology · 2025Review
- Clinical Response Characteristics of Salivary Proteins in the Management Strategy of Diabetes-Associated Periodontitis.Journal of proteome research · 2025Article
- Mass Spectrometry-Based Proteomics Analysis Unveils PTPRS Inhibits Proliferation and Inflammatory Response of Keratinocytes in Psoriasis.Inflammation · 2025Article
- Comparative Proteomics Analysis Reveals Distinct Molecular Phenotype and Biomarkers in Patients with Erythrodermic Atopic Dermatitis and Erythrodermic Psoriasis.Inflammation · 2025Article
- Proteomic analysis of cardiovascular disease-associated proteins in Korean patients with moderate-to-severe atopic dermatitis.The World Allergy Organization journal · 2024Article
- Suppression of TCF4 promotes a ZC3H12A-mediated self-sustaining inflammatory feedback cycle involving IL-17RA/IL-17RE epidermal signaling.JCI insight · 2024Article
- Comparative analyses of Netherton syndrome patients and Spink5 conditional knock-out mice uncover disease-relevant pathways.Communications biology · 2024Article
- IL-23 induces CLEC5AJournal of autoimmunity · 2024Article
- Granzyme K mediates IL-23-dependent inflammation and keratinocyte proliferation in psoriasis.Frontiers in immunology · 2024Article
- Retrospective pharmacogenetic study of psoriasis highlights the role of KLK7 in tumour necrosis factor signalling.The British journal of dermatology · 2023Article
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Authors and funding
21 authors at 6 institutions in 2 countries.
Funding
Abstract
Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease hypothesized to promote inflammation via cleavage of protease-activated receptor 1 (PAR1) and PAR2. KLK6 levels are elevated in multiple inflammatory and autoimmune conditions, but no definitive role in pathogenesis has been established. Here, we show that skin-targeted overexpression of KLK6 causes generalized, severe psoriasiform dermatitis with spontaneous development of debilitating psoriatic arthritis-like joint disease. The psoriatic skin and joint phenotypes are reversed by normalization of skin KLK6 levels and attenuated following genetic elimination of PAR1 but not PAR2. Conservation of this regulatory pathway was confirmed in human psoriasis using vorapaxar, an FDA-approved PAR1 antagonist, on explanted lesional skin from patients with psoriasis. Beyond defining a critical role for KLK6/PAR1 signaling in promoting psoriasis, our results demonstrate that KLK6/PAR1-mediated inflammation in the skin alone is sufficient to drive inflammatory joint disease. Further, we identify PAR1 as a promising cytokine-independent target in therapy of psoriasis and psoriatic arthritis.
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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.