Evidence map›Paper›PMID 41436824›Full record

ArticleScientific reports2025

Probing the activity of cysteine cathepsins in inflammatory bowel diseases.

Bethany M Anderson, Alexander R Ziegler, Rhiannon I Campden, Hongyi Wu, Bangyan Xu, Rachel M McQuade, Simona E Carbone, Daniel P Poole, Alan E Lomax, David E Reed and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Faecal Cathepsin B and S Are Associated With Liver Disease Severity and Adiposity in MASLD.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Bethany M AndersonDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia.
Alexander R ZieglerDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia.
Rhiannon I CampdenSnyder Institute for Chronic Disease and Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada.
Hongyi WuDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia.
Bangyan XuDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia.
Rachel M McQuadeDepartment of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, Australia.
Simona E CarboneDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
Daniel P PooleDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
Alan E LomaxDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
David E ReedDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
Stephen J VannerDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
Robin M YatesSnyder Institute for Chronic Disease and Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada.
Nigel W BunnettDepartment of Molecular Pathobiology, New York University College of Dentistry, New York, NY, USA.
Laura E Edgington-MitchellDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia. laura.edgingtonmitchell@unimelb.edu.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cathepsin S is a cysteine protease that has been implicated in inflammatory bowel diseases (IBD) for its ability to promote visceral pain. Given its pro-inflammatory roles, we hypothesized that cathepsin S would drive other symptoms associated with IBD. Using activity-based probes, we investigated cysteine cathepsin activation in human and murine colitis. We observed a significant increase in fecal cathepsin S in patients with ulcerative colitis compared to healthy controls, while cathepsin S in mucosal biopsies was unchanged. Mice with experimental colitis exhibited a modest increase in mucosal activity of both cathepsin S and X compared to naïve mice. Luminal secretion of cathepsin S was dramatically increased upon colitis induction, although differences between mouse colonies were observed. To investigate the contribution of cathepsin S and cathepsin X to colitis, we induced colitis in cathepsin-deficient mice. Cathepsin X-deficient mice exhibited no clear differences in disease indicators compared to wild-type mice. While cathepsin S-deficient mice exhibited less rectal bleeding, less splenomegaly and marginally improved histological scores, weight loss, diarrhea, colon shortening, and myeloperoxidase activity were not significantly different from wild-type mice. To determine whether pharmacologic inhibition of cathepsin S activity would ameliorate symptoms of colitis, a reversible inhibitor LY3000328 was administered to mice at the initiation of colitis. LY3000328 provoked a clear upregulation of cathepsin S and L activity in the mucosa, most likely through a compensatory mechanism. This increase in protease activity was associated with exacerbated histological scores and slight splenomegaly. Collectively, these results suggest that cathepsin S, but not cathepsin X, may contribute to some of the symptoms of experimental colitis. While cathepsin S has potential to be a therapeutic target in colitis, improved strategies to sustain its inhibition are required in future.

Indexed as

CathepsinsInflammatory Bowel DiseasesAdultAnimalsColitisColitis, UlcerativeColonDisease Models, AnimalFecesFemaleHumansIntestinal MucosaMaleMiceMice, Inbred C57BLMice, Knockoutcathepsin SCathepsinsActivity-based probesCathepsinColitisFunctional imagingInflammatory bowel diseaseProtease

Identifiers

PMID41436824
PMCPMC12824247

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.