Claudins: Beyond Tight Junctions in Human IBD and Murine Models

Scientific paper - Original scientific paper

• Author: Snježana Čužić
• Author: Maja Antolić
• Author: Anja Ognjenović
• Author: Darija Stupin-Polančec
• Author: Adriana Petrinić Grba
• Author: Boška Hrvačić
• Author: Miroslava Dominis Kramarić
• Author: Sanja Musladin
• Author: Lidija Požgaj
• Author: Ivo Zlatar
• Author: Denis Polančec
• Author: Gorana Aralica
• Author: Marko Banić
• Author: Marija Urek
• Author: Brankica Mijandrušić Sinčić
• Author: Aleksandar Čubranić
• Author: Ines Glojnarić
• Author: Martina Bosnar
• Author: Vesna Eraković Haber
• Author's institution: University of Zagreb; School of Medicine; (Department of Internal Medicine)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract (english)

Claudins are transmembrane proteins constituting one of three tight junction protein families. In patients with inflammatory bowel disease (IBD), disease activity–dependent changes in expression of certain claudins have been noted, thus making certain claudin family members potential therapy targets. A study was undertaken with the aim of exploring expression of claudins in human disease and two different animal models of IBD: dextrane sulfate sodium–induced colitis and adoptive transfer model of colitis. The expression of sealing claudin-1, claudin-3, claudin-4, and claudin-8, and pore-forming claudin-2 in humans and rodents has been evaluated by immunohistochemistry and quantitative polymerase chain reaction. Claudins were expressed by epithelial and cells of mesodermal origin and were found to be situated at the membrane, within the cytoplasm, or within the nuclei. Claudin expression by human mononuclear cells isolated from lamina propria has been confirmed by Western blot and flow cytometry. The claudin expression pattern in uninflamed and inflamed colon varied between species and murine strains. In IBD and both animal models, diverse alterations in claudin expression by epithelial and inflammatory cells were recorded. Tissue mRNA levels for each studied claudin reflected changes within cell lineage and, at the same time, mirrored the ratio between various cell types. Based on the results of the study, it can be concluded that 1) claudins are not expressed exclusively by epithelial cells, but by certain types of cells of mesodermal origin as well; 2) changes in the claudin mRNA level should be interpreted in the context of overall tissue alterations; and 3) both IBD animal models that were analyzed can be used for investigating claudins as a therapy target, respecting their similarities and differences highlighted in this study.

• Keywords (english): Crohn’s disease; adoptive transfer colitis model; claudins; dextran sodium sulfate colitis model; inflammatory bowel disease; ulcerative colitis
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Frontiers in Pharmacology
• Numbering: vol. 12, 682614
• e-ISSN: 1663-9812
• DOI: https://doi.org/10.3389/fphar.2021.682614
• URN:NBN: urn:nbn:hr:105:782656
• Publication: 2021-11-17
• Document URL: https://www.frontiersin.org/articles/10.3389/fphar.2021.682614/full
• Type of resource: Text
• Access conditions: Open access
• Created on: 2022-02-03 11:36:36