Characterizing the human intestinal chondroitin sulfate glycosaminoglycan sulfation signature in inflammatory bowel disease.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
23 05 2024
Historique:
received: 21 12 2023
accepted: 29 04 2024
medline: 24 5 2024
pubmed: 24 5 2024
entrez: 23 5 2024
Statut: epublish

Résumé

The intestinal extracellular matrix (ECM) helps maintain appropriate tissue barrier function and regulate host-microbial interactions. Chondroitin sulfate- and dermatan sulfate-glycosaminoglycans (CS/DS-GAGs) are integral components of the intestinal ECM, and alterations in CS/DS-GAGs have been shown to significantly influence biological functions. Although pathologic ECM remodeling is implicated in inflammatory bowel disease (IBD), it is unknown whether changes in the intestinal CS/DS-GAG composition are also linked to IBD in humans. Our aim was to characterize changes in the intestinal ECM CS/DS-GAG composition in intestinal biopsy samples from patients with IBD using mass spectrometry. We characterized intestinal CS/DS-GAGs in 69 pediatric and young adult patients (n = 13 control, n = 32 active IBD, n = 24 IBD in remission) and 6 adult patients. Here, we report that patients with active IBD exhibit a significant decrease in the relative abundance of CS/DS isomers associated with matrix stability (CS-A and DS) compared to controls, while isomers implicated in matrix instability and inflammation (CS-C and CS-E) were significantly increased. This imbalance of intestinal CS/DS isomers was restored among patients in clinical remission. Moreover, the abundance of pro-stabilizing CS/DS isomers negatively correlated with clinical disease activity scores, whereas both pro-inflammatory CS-C and CS-E content positively correlated with disease activity scores. Thus, pediatric patients with active IBD exhibited increased pro-inflammatory and decreased pro-stabilizing CS/DS isomer composition, and future studies are needed to determine whether changes in the CS/DS-GAG composition play a pathogenic role in IBD.

Identifiants

pubmed: 38782973
doi: 10.1038/s41598-024-60959-x
pii: 10.1038/s41598-024-60959-x
doi:

Substances chimiques

Chondroitin Sulfates 9007-28-7
Glycosaminoglycans 0
chondroitin sulfate glycosaminoglycan 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

11839

Subventions

Organisme : NIDDK NIH HHS
ID : DK131695
Pays : United States
Organisme : NIDDK NIH HHS
ID : DK089056
Pays : United States
Organisme : NIDDK NIH HHS
ID : DK101997
Pays : United States
Organisme : NIDDK NIH HHS
ID : DK017047
Pays : United States
Organisme : NIDDK NIH HHS
ID : DK114474
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM127579
Pays : United States
Organisme : National Institute of Allergy and Infectious Diseases
ID : AI171150
Organisme : NIA NIH HHS
ID : R21 AG074152
Pays : United States
Organisme : U.S. Department of Defense
ID : W81XWH2110635
Organisme : Office of Research Central, University of Washington
ID : A139339

Informations de copyright

© 2024. The Author(s).

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Auteurs

Kendra L Francis (KL)

Department of Pediatric Gastroenterology and Hepatology, Seattle Children's Hospital, Seattle, WA, USA.
Department of Medicine, University of Washington Medicine Diabetes Institute, 750 Republican St, Box 358062, Seattle, WA, 98195, USA.

Hengqi B Zheng (HB)

Department of Pediatric Gastroenterology and Hepatology, Seattle Children's Hospital, Seattle, WA, USA.

David L Suskind (DL)

Department of Pediatric Gastroenterology and Hepatology, Seattle Children's Hospital, Seattle, WA, USA.

Taylor A Murphree (TA)

Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA.

Bao Anh Phan (BA)

Department of Medicine, University of Washington Medicine Diabetes Institute, 750 Republican St, Box 358062, Seattle, WA, 98195, USA.

Emily Quah (E)

Department of Medicine, University of Washington Medicine Diabetes Institute, 750 Republican St, Box 358062, Seattle, WA, 98195, USA.

Aarun S Hendrickson (AS)

Department of Medicine, University of Washington Medicine Diabetes Institute, 750 Republican St, Box 358062, Seattle, WA, 98195, USA.

Xisheng Zhou (X)

Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA.

Mason Nuding (M)

Department of Pediatric Gastroenterology and Hepatology, Seattle Children's Hospital, Seattle, WA, USA.

Alexandra S Hudson (AS)

Department of Pediatric Gastroenterology and Hepatology, Seattle Children's Hospital, Seattle, WA, USA.

Miklos Guttman (M)

Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA.

Gregory J Morton (GJ)

Department of Medicine, University of Washington Medicine Diabetes Institute, 750 Republican St, Box 358062, Seattle, WA, 98195, USA.

Michael W Schwartz (MW)

Department of Medicine, University of Washington Medicine Diabetes Institute, 750 Republican St, Box 358062, Seattle, WA, 98195, USA.

Kimberly M Alonge (KM)

Department of Medicine, University of Washington Medicine Diabetes Institute, 750 Republican St, Box 358062, Seattle, WA, 98195, USA.
Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA.

Jarrad M Scarlett (JM)

Department of Pediatric Gastroenterology and Hepatology, Seattle Children's Hospital, Seattle, WA, USA. jarrad.scarlett@seattlechildrens.org.
Department of Medicine, University of Washington Medicine Diabetes Institute, 750 Republican St, Box 358062, Seattle, WA, 98195, USA. jarrad.scarlett@seattlechildrens.org.

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