Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Jul;65(7):1215-24.
doi: 10.1136/gutjnl-2015-309147. Epub 2016 Apr 12.

Protease inhibition as new therapeutic strategy for GI diseases

Nathalie Vergnolle  1
Affiliations
Review

Protease inhibition as new therapeutic strategy for GI diseases

Nathalie Vergnolle. Gut. 2016 Jul.

Abstract

The GI tract is the most exposed organ to proteases, both in physiological and pathophysiological conditions. For digestive purposes, the lumen of the upper GI tract contains large amounts of pancreatic proteases, but studies have also demonstrated increased proteolytic activity into mucosal tissues (both in the upper and lower GI tract), associated with pathological conditions. This review aims at outlining the evidences for dysregulated proteolytic homeostasis in GI diseases and the pathogenic mechanisms of increased proteolytic activity. The therapeutic potential of protease inhibition in GI diseases is discussed, with a particular focus on IBDs, functional GI disorders and colorectal cancer.

Keywords: ENZYMOLOGY; INFLAMMATORY BOWEL DISEASE; INFLAMMATORY BOWEL SYNDROME; INFLAMMATORY MECHANISMS.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Representation of human cell proteases according to their catalytic mechanism and their intracellular or extracellular representation. MMPs, matrix metalloproteinases.
Figure 2
Figure 2
Source of proteases in the GI tract.
Figure 3
Figure 3
In situ proteolytic activity (elastolytic in A, trypsin-like in B) performed as previously described in ref. , in human colons of healthy individuals, patients with IBS and patients with Crohn's disease.
Figure 4
Figure 4
Mechanism of action of proteases in GI diseases. PAR, protease-activated receptor.
See this image and copyright information in PMC

References

    1. Motta JP, Martin L, Vergnolle N. Proteases/antiproteases in inflammatory bowel diseases. In: Vergnolle N, Chignard M. Proteases and their receptors in inflammation. Basel: Springer, 2011:173–215.
    1. Carroll IM, Maharshak N. Enteric bacterial proteases in inflammatory bowel disease—pathophysiology and clinical implications. World J Gastroenterol 2013;19:7531–43. 10.3748/wjg.v19.i43.7531 - DOI - PMC - PubMed
    1. Knecht W, Cottrell GS, Amadesi S, et al. . Trypsin IV or mesotrypsin and p23 cleave protease-activated receptors 1 and 2 to induce inflammation and hyperalgesia. J Biol Chem 2007;282:26089–100. 10.1074/jbc.M703840200 - DOI - PubMed
    1. Pederzoli-Ribeil M, Gabillet J, Witko-Sarsat V. Proteases from inflammatory cells: regulation of inflammatory response. In: Vergnolle N, Chignard M. Proteases and their receptors in inflammation. Basel: Springer, 2011:73–100.
    1. Segel GB, Halterman MW, Lichtman MA. The paradox of the neutrophil's role in tissue injury. J Leukoc Biol 2011;89:359–72. 10.1189/jlb.0910538 - DOI - PMC - PubMed

Publication types

MeSH terms