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

Scientific Reports
Alexandre Denadai-SouzaCéline Deraison

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 approac...Continue Reading

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Datasets Mentioned

BETA
PXD009450

Methods Mentioned

BETA
zymography
electrophoresis
proteomic profiling
biopsy
biopsies
proteomic
acetylation
PCR

Clinical Trials Mentioned

NCT01990716

Software Mentioned

Image Lab
Xcalibur
Andromeda
MaxQuant

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