ArticleScientific reports2017
Cathepsin S inhibition combines control of systemic and peripheral pathomechanisms of autoimmune tissue injury.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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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
33 citing papers in PubMed, 62 citations in OpenAlex.
- First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ASP1617, a Cathepsin-S Inhibitor, in Healthy Adult Subjects.Clinical and translational science · 2026Trial
- A randomized, double-blind, placebo-controlled, multiple dose, parallel study to investigate the effects of a cathepsin S inhibitor in celiac disease.Clinical and translational science · 2025Trial
- A randomized, double-blind, placebo-controlled, parallel group study on the effects of a cathepsin S inhibitor in primary Sjögren's syndrome.Rheumatology (Oxford, England) · 2023Trial
- Epstein Barr virus antigen-induced autoantibodies against complement C1q exacerbate renal disease in lupus-prone mice.Frontiers in immunology · 2026Article
- Cathepsin S: a double-edged protease in barrier damage, neuroimmune inflammation, and tissue repair, with implications for dermatology.Frontiers in immunology · 2026Review
- Exploring the role of Cathepsin S in mitochondrial energy metabolism: implications for cancer progression and therapeutic targeting.Medical oncology (Northwood, London, England) · 2025Review
- The pH-Dependent Specificity of Cathepsin S and Its Implications for Inflammatory Communications and Disease.Biochemistry · 2025Article
- Cathepsins: Emerging targets in the tumor ecosystem to overcome cancers.Seminars in cancer biology · 2025Review
- The Many Faces of Protease-Activated Receptor 2 in Kidney Injury.Biomedicines · 2025Review
- The multifaceted roles of cathepsins in immune and inflammatory responses: implications for cancer therapy, autoimmune diseases, and infectious diseases.Biomarker research · 2024Review
- Advances in Cathepsin S Inhibition: Challenges and Breakthroughs in Drug Development.Pathophysiology : the official journal of the International Society for Pathophysiology · 2024Review
- Effects of Cathepsin S Inhibition in the Age-Related Dry Eye Phenotype.Investigative ophthalmology & visual science · 2023Article
- Retinal transcriptome profiling identifies novel candidate genes associated with visual impairment in a mouse model of multiple sclerosis.Animal cells and systems · 2023Article
- Kinetic Characterization of Cerium and Gallium Ions as Inhibitors of Cysteine Cathepsins L, K, and S.International journal of molecular sciences · 2022Article
- Discovery of anti-Formin-like 1 protein (FMNL1) antibodies in membranous nephropathy and other glomerular diseases.Scientific reports · 2022Article
- Lysosomes in Stem Cell Quiescence: A Potential Therapeutic Target in Acute Myeloid Leukemia.Cancers · 2022Review
- Cathepsin S is a novel target for age-related dry eye.Experimental eye research · 2022Article
- Targeting lysosomes in human disease: from basic research to clinical applications.Signal transduction and targeted therapy · 2021Review
- Population pharmacokinetic analysis of RO5459072, a low water-soluble drug exhibiting complex food-drug interactions.British journal of clinical pharmacology · 2021Article
- Overexpression of cathepsin S exacerbates lupus pathogenesis through upregulation TLR7 and IFN-α in transgenic mice.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cathepsin(Cat)-S processing of the invariant chain-MHC-II complex inside antigen presenting cells is a central pathomechanism of autoimmune-diseases. Additionally, Cat-S is released by activated-myeloid cells and was recently described to activate protease-activated-receptor-(PAR)-2 in extracellular compartments. We hypothesized that Cat-S blockade targets both mechanisms and elicits synergistic therapeutic effects on autoimmune tissue injury. MRL-(Fas)lpr mice with spontaneous autoimmune tissue injury were treated with different doses of Cat-S inhibitor RO5459072, mycophenolate mofetil or vehicle. Further, female MRL-(Fas)lpr mice were injected with recombinant Cat-S with/without concomitant Cat-S or PAR-2 blockade. Cat-S blockade dose-dependently reversed aberrant systemic autoimmunity, e.g. plasma cytokines, activation of myeloid cells and hypergammaglobulinemia. Especially IgG autoantibody production was suppressed. Of note (MHC-II-independent) IgM were unaffected by Cat-S blockade while they were suppressed by MMF. Cat-S blockade dose-dependently suppressed immune-complex glomerulonephritis together with a profound and early effect on proteinuria, which was not shared by MMF. In fact, intravenous Cat-S injection induced severe glomerular endothelial injury and albuminuria, which was entirely prevented by Cat-S or PAR-2 blockade. In-vitro studies confirm that Cat-S induces endothelial activation and injury via PAR-2. Therapeutic Cat-S blockade suppresses systemic and peripheral pathomechanisms of autoimmune tissue injury, hence, Cat-S is a promising therapeutic target in lupus nephritis.
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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.