Functional Proteomic Profiling of Secreted Serine Proteases in Health and Inflammatory Bowel Disease

Alexandre Denadai-Souza, Chrystelle Bonnart, Núria Solà Tapias, Marlène Marcellin, Brendan Gilmore, Laurent Alric, Delphine Bonnet, Odile Burlet-Schiltz, Morley D. Hollenberg, Nathalie Vergnolle*, Céline Deraison

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Citations (Scopus)
40 Downloads (Pure)

Abstract

While proteases are essential in gastrointestinal physiology, accumulating evidence indicates that dysregulated proteolysis plays a pivotal role in the pathophysiology of inflammatory bowel disease (IBD). Nonetheless, the identity of overactive proteases released by human colonic mucosa remains largely unknown. Studies of protease abundance have primarily investigated expression profiles, not taking into account their enzymatic activity. Herein we have used serine protease-targeted activity-based probes (ABPs) coupled with mass spectral analysis to identify active forms of proteases secreted by the colonic mucosa of healthy controls and IBD patients. Profiling of (Pro-Lys)-ABP bound proteases revealed that most of hyperactive proteases from IBD secretome are clustered at 28-kDa. We identified seven active proteases: the serine proteases cathepsin G, plasma kallikrein, plasmin, tryptase, chymotrypsin-like elastase 3 A, and thrombin and the aminopeptidase B. Only cathepsin G and thrombin were overactive in supernatants from IBD patient tissues compared to healthy controls. Gene expression analysis highlighted the transcription of genes encoding these proteases into intestinal mucosae. The functional ABP-targeted proteomic approach that we have used to identify active proteases in human colonic samples bears directly on the understanding of the role these enzymes may play in the pathophysiology of IBD.

Original languageEnglish
Article number7834
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 01 Dec 2018

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Functional Proteomic Profiling of Secreted Serine Proteases in Health and Inflammatory Bowel Disease'. Together they form a unique fingerprint.

Cite this