Proteomics-Informed Identification of Luminal Targets For In Situ Diagnosis of Inflammatory Bowel Disease.

Biomarker(s) Caco-2 cells Colon Gastrointestinal tract Inflammatory bowel disease (IBD) In vitro model(s) Nanoparticle(s) Principal component analysis Proteomic Targeted drug delivery

Journal

Journal of pharmaceutical sciences
ISSN: 1520-6017
Titre abrégé: J Pharm Sci
Pays: United States
ID NLM: 2985195R

Informations de publication

Date de publication:
01 2021
Historique:
received: 20 08 2020
revised: 01 11 2020
accepted: 02 11 2020
pubmed: 8 11 2020
medline: 22 6 2021
entrez: 7 11 2020
Statut: ppublish

Résumé

Inflammatory bowel disease (IBD) is a chronic condition resulting in impaired intestinal homeostasis. Current practices for diagnosis of IBD are challenged by invasive, demanding procedures. We hypothesized that proteomics analysis could provide a powerful tool for identifying clinical biomarkers for non-invasive IBD diagnosis. Here, the global intestinal proteomes from commonly used in vitro and in vivo models of IBD were analyzed to identify apical and luminal proteins that can be targeted by orally delivered diagnostic agents. Global proteomics analysis revealed upregulated plasma membrane proteins in intestinal segments of proximal- and distal colon from dextran sulfate sodium-treated mice and also in inflamed human intestinal Caco-2 cells pretreated with pro-inflammatory agents. The upregulated colon proteins in mice were compared to the proteome of the healthy ileum, to ensure targeting of diagnostic agents to the inflamed colon. Promising target proteins for future investigations of non-invasive diagnosis of IBD were found in both systems and included Tgm2/TGM2, Icam1/ICAM1, Ceacam1/CEACAM1, and Anxa1/ANXA1. Ultimately, these findings will guide the selection of appropriate antibodies for surface functionalization of imaging agents aimed to target inflammatory biomarkers in situ.

Identifiants

pubmed: 33159915
pii: S0022-3549(20)30685-7
doi: 10.1016/j.xphs.2020.11.001
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

239-250

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Shno Asad (S)

Department of Pharmacy, Science for Life Laboratory, Uppsala University, SE-75123 Uppsala, Sweden.

Christine Wegler (C)

Department of Pharmacy, Uppsala University, SE-75123 Uppsala, Sweden; Department of Pharmacy, Uppsala University Drug Optimization and Pharmaceutical Profiling Platform (UDOPP), SE-75123 Uppsala, Sweden.

David Ahl (D)

Department of Medical Cell Biology, Uppsala University, SE-75123 Uppsala, Sweden.

Christel A S Bergström (CAS)

Department of Pharmacy, Uppsala University, SE-75123 Uppsala, Sweden; The Swedish Drug Delivery Center, Department of Pharmacy, Uppsala University, SE-75123 Uppsala, Sweden.

Mia Phillipson (M)

Department of Medical Cell Biology, Uppsala University, SE-75123 Uppsala, Sweden.

Per Artursson (P)

Department of Pharmacy, Uppsala University, SE-75123 Uppsala, Sweden.

Alexandra Teleki (A)

Department of Pharmacy, Science for Life Laboratory, Uppsala University, SE-75123 Uppsala, Sweden. Electronic address: alexandra.teleki@scilifelab.uu.se.

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Classifications MeSH