Evidence map›Paper›PMID 31066456›Full record

ArticleInflammatory bowel diseases2019

Persistent Salmonella enterica Serovar Typhimurium Infection Induces Protease Expression During Intestinal Fibrosis.

Katrin Ehrhardt, Natalie Steck, Reinhild Kappelhoff, Stephanie Stein, Florian Rieder, Ilyssa O Gordon, Erin C Boyle, Peter Braubach, Christopher M Overall, B Brett Finlay and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Inflammatory bowel diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.4field-weighted citation impact, top 13% of its field
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

12 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Autophagy · 2025
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  5. Review
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  8. Cross-Talk Between the Intestinal Epithelium andFrontiers in microbiology · 2022
    Review
  9. Mechanisms for the Invasion and Dissemination ofThe Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2022
    Review
  10. Review
  11. Article
  12. Scientific reports · 2020
    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

11 authors at 4 institutions in 3 countries.

Katrin EhrhardtInstitute of Medical Microbiology and Hospital Epidemiology and German Center for Infection Research (DZIF), Partner Site Hannover, Hannover Medical School, Hannover, Germany.
Natalie SteckInstitute for Experimental Medicine, Christian-Albrechts University of Kiel, Kiel, Germany, and Research Center Borstel, Borstel, Germany.
Reinhild KappelhoffDepartment of Oral Biological and Medical Sciences, Centre for Blood Research, Faculty of Dentistry, University of British Columbia, Vancouver, BC, Canada.
Stephanie SteinInstitute for Experimental Medicine, Christian-Albrechts University of Kiel, Kiel, Germany, and Research Center Borstel, Borstel, Germany.
Florian RiederDepartment of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute.
Ilyssa O GordonDepartment of Pathology, Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Erin C BoyleDepartment of Cardiothoracic, Transplantation, and Vascular Surgery, Hannover Medical School, Hannover, Germany.
Peter BraubachInstitute for Pathology, Hannover Medical School, Hannover, Germany.
Christopher M OverallDepartment of Oral Biological and Medical Sciences, Centre for Blood Research, Faculty of Dentistry, University of British Columbia, Vancouver, BC, Canada.
B Brett FinlayMichael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.
Guntram A GrasslInstitute of Medical Microbiology and Hospital Epidemiology and German Center for Infection Research (DZIF), Partner Site Hannover, Hannover Medical School, Hannover, Germany.
Medizinische Hochschule Hannover · DEUniversity of British Columbia · CAChristian-Albrechts-Universität zu Kiel · DECleveland Clinic · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIntestinal fibrosis is a common and serious complication of Crohn's disease characterized by the accumulation of fibroblasts, deposition of extracellular matrix, and formation of scar tissue. Although many factors including cytokines and proteases contribute to the development of intestinal fibrosis, the initiating mechanisms and the complex interplay between these factors remain unclear.

methodsChronic infection of mice with Salmonella enterica serovar Typhimurium was used to induce intestinal fibrosis. A murine protease-specific CLIP-CHIP microarray analysis was employed to assess regulation of proteases and protease inhibitors. To confirm up- or downregulation during fibrosis, we performed quantitative real-time polymerase chain reaction (PCR) and immunohistochemical stainings in mouse tissue and tissue from patients with inflammatory bowel disease. In vitro infections were used to demonstrate a direct effect of bacterial infection in the regulation of proteases.

resultsMice develop severe and persistent intestinal fibrosis upon chronic infection with Salmonella enterica serovar Typhimurium, mimicking the pathology of human disease. Microarray analyses revealed 56 up- and 40 downregulated proteases and protease inhibitors in fibrotic cecal tissue. Various matrix metalloproteases, serine proteases, cysteine proteases, and protease inhibitors were regulated in the fibrotic tissue, 22 of which were confirmed by quantitative real-time PCR. Proteases demonstrated site-specific staining patterns in intestinal fibrotic tissue from mice and in tissue from human inflammatory bowel disease patients. Finally, we show in vitro that Salmonella infection directly induces protease expression in macrophages and epithelial cells but not in fibroblasts.

conclusionsIn summary, we show that chronic Salmonella infection regulates proteases and protease inhibitors during tissue fibrosis in vivo and in vitro, and therefore this model is well suited to investigating the role of proteases in intestinal fibrosis.

Indexed as

AnimalsCytokinesFibrosisGene Expression ProfilingIntestinal DiseasesMacrophagesMiceMice, Inbred C57BLNIH 3T3 CellsPeptide HydrolasesProtease InhibitorsSalmonella entericaSalmonella Infections, AnimalCytokinesPeptide HydrolasesProtease Inhibitorsinflammationintestinal fibrosisproteasesSalmonella

Identifiers

PMID31066456
PMCPMC6749888
OpenAlexW2944371379

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.