ArticleGastroenterology2011
Cathepsin S is activated during colitis and causes visceral hyperalgesia by a PAR2-dependent mechanism in mice.
Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 99 citations in OpenAlex.
- Monoclonal antibody inhibition of PAR2 reduces phenotype severity and pain in murine inflammatory bowel disease.Pain reports · 2026Article
- Protease-Activated Receptor-2 Promotes Metastasis: An Emerging Therapeutic Target.Molecular cancer research : MCR · 2026Review
- Mechanisms of chronic abdominal pain in inflammatory bowel disease and implications for treatment.Nature reviews. Gastroenterology & hepatology · 2026Review
- Electrophysiological and Proteomic Evidence of Protease-Mediated Pro-nociceptive Signaling in Inflammatory Bowel Disease Patients.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Proteases in intestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Proteases and Abdominal Pain-Old Dog, New (Microbial) Tricks.Cellular and molecular gastroenterology and hepatology · 2026Review
- Probing the activity of cysteine cathepsins in inflammatory bowel diseases.Scientific reports · 2025Article
- Nanomedicines targeting protease-activated receptor 2 in endosomes provide sustained analgesia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A Bacteroides fragilis protease activates host PARCell host & microbe · 2025Article
- The gut-brain axis and pain signalling mechanisms in the gastrointestinal tract.Nature reviews. Gastroenterology & hepatology · 2025Review
- Identification of a secreted protease frombioRxiv : the preprint server for biology · 2025Article
- A New Strategy in Modulating the Protease-Activated Receptor 2 (Par2) in Autoimmune Diseases.International journal of molecular sciences · 2025Review
- Cathepsin S: molecular mechanisms in inflammatory and immunological processes.Frontiers in immunology · 2025Review
- Integrating single-cell RNA-Seq and machine learning to dissect tryptophan metabolism in ulcerative colitis.Journal of translational medicine · 2024Article
- Protease-Activated Receptor 2 (PAR2) Expressed in Sensory Neurons Contributes to Signs of Pain and Neuropathy in Paclitaxel Treated Mice.The journal of pain · 2023Article
- Chemical Tools to Image the Activity of PAR-Cleaving Proteases.ACS bio & med chem Au · 2023Review
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Mice expressing fluorescent PARProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Tumor Cell-Induced Platelet Aggregation as an Emerging Therapeutic Target for Cancer Therapy.Frontiers in oncology · 2022Review
- Molecular probes for selective detection of cysteine cathepsins.Organic & biomolecular chemistry · 2021Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsAlthough proteases control inflammation and pain, the identity, cellular origin, mechanism of action, and causative role of proteases that are activated during disease are not defined. We investigated the activation and function of cysteine cathepsins (Cat) in colitis.
methodsBecause protease activity, rather than expression, is regulated, we treated mice with fluorescent activity-based probes that covalently modify activated cathepsins. Activated proteases were localized by tomographic imaging of intact mice and confocal imaging of tissues, and were identified by electrophoresis and immunoprecipitation. We examined the effects of activated cathepsins on excitability of colonic nociceptors and on colonic pain, and determined their role in colonic inflammatory pain by gene deletion.
resultsTomography and magnetic resonance imaging localized activated cathepsins to the inflamed colon of piroxicam-treated il10(-/-) mice. Confocal imaging detected activated cathepsins in colonic macrophages and spinal neurons and microglial cells of mice with colitis. Gel electrophoresis and immunoprecipitation identified activated Cat-B, Cat-L, and Cat-S in colon and spinal cord, and Cat-S was preferentially secreted into the colonic lumen. Intraluminal Cat-S amplified visceromotor responses to colorectal distension and induced hyperexcitability of colonic nociceptors, which required expression of protease-activated receptor-2. Cat-S deletion attenuated colonic inflammatory pain induced with trinitrobenzene sulfonic acid.
conclusionsActivity-based probes enable noninvasive detection, cellular localization, and proteomic identification of proteases activated during colitis and are potential diagnostic tools for detection of predictive disease biomarkers. Macrophage cathepsins are activated during colitis, and Cat-S activates nociceptors to induce visceral pain via protease-activated receptor-2. Cat-S mediates colitis pain and is a potential therapeutic target.
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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.