Claudins: Beyond Tight Junctions in Human IBD and Murine Models
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...
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2021
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oai:doaj.org-article:08d266c4a2644bd6848be78913f1a5f42021-11-17T06:50:44ZClaudins: Beyond Tight Junctions in Human IBD and Murine Models1663-981210.3389/fphar.2021.682614https://doaj.org/article/08d266c4a2644bd6848be78913f1a5f42021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.682614/fullhttps://doaj.org/toc/1663-9812Claudins 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.Snježana ČužićMaja AntolićAnja OgnjenovićDarija Stupin-PolančecAdriana Petrinić GrbaBoška HrvačićMiroslava Dominis KramarićSanja MusladinLidija PožgajIvo ZlatarDenis PolančecGorana AralicaGorana AralicaMarko BanićMarko BanićMarko BanićMarija UrekMarija UrekBrankica Mijandrušić SinčićBrankica Mijandrušić SinčićAleksandar ČubranićAleksandar ČubranićInes GlojnarićMartina BosnarVesna Eraković HaberVesna Eraković HaberFrontiers Media S.A.articleclaudinsinflammatory bowel diseasedextran sodium sulfate colitis modeladoptive transfer colitis modelulcerative colitisCrohn’s diseaseTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021) |
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claudins inflammatory bowel disease dextran sodium sulfate colitis model adoptive transfer colitis model ulcerative colitis Crohn’s disease Therapeutics. Pharmacology RM1-950 |
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claudins inflammatory bowel disease dextran sodium sulfate colitis model adoptive transfer colitis model ulcerative colitis Crohn’s disease Therapeutics. Pharmacology RM1-950 Snježana Čužić Maja Antolić Anja Ognjenović Darija Stupin-Polančec Adriana Petrinić Grba Boška Hrvačić Miroslava Dominis Kramarić Sanja Musladin Lidija Požgaj Ivo Zlatar Denis Polančec Gorana Aralica Gorana Aralica Marko Banić Marko Banić Marko Banić Marija Urek Marija Urek Brankica Mijandrušić Sinčić Brankica Mijandrušić Sinčić Aleksandar Čubranić Aleksandar Čubranić Ines Glojnarić Martina Bosnar Vesna Eraković Haber Vesna Eraković Haber Claudins: Beyond Tight Junctions in Human IBD and Murine Models |
| description |
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. |
| format |
article |
| author |
Snježana Čužić Maja Antolić Anja Ognjenović Darija Stupin-Polančec Adriana Petrinić Grba Boška Hrvačić Miroslava Dominis Kramarić Sanja Musladin Lidija Požgaj Ivo Zlatar Denis Polančec Gorana Aralica Gorana Aralica Marko Banić Marko Banić Marko Banić Marija Urek Marija Urek Brankica Mijandrušić Sinčić Brankica Mijandrušić Sinčić Aleksandar Čubranić Aleksandar Čubranić Ines Glojnarić Martina Bosnar Vesna Eraković Haber Vesna Eraković Haber |
| author_facet |
Snježana Čužić Maja Antolić Anja Ognjenović Darija Stupin-Polančec Adriana Petrinić Grba Boška Hrvačić Miroslava Dominis Kramarić Sanja Musladin Lidija Požgaj Ivo Zlatar Denis Polančec Gorana Aralica Gorana Aralica Marko Banić Marko Banić Marko Banić Marija Urek Marija Urek Brankica Mijandrušić Sinčić Brankica Mijandrušić Sinčić Aleksandar Čubranić Aleksandar Čubranić Ines Glojnarić Martina Bosnar Vesna Eraković Haber Vesna Eraković Haber |
| author_sort |
Snježana Čužić |
| title |
Claudins: Beyond Tight Junctions in Human IBD and Murine Models |
| title_short |
Claudins: Beyond Tight Junctions in Human IBD and Murine Models |
| title_full |
Claudins: Beyond Tight Junctions in Human IBD and Murine Models |
| title_fullStr |
Claudins: Beyond Tight Junctions in Human IBD and Murine Models |
| title_full_unstemmed |
Claudins: Beyond Tight Junctions in Human IBD and Murine Models |
| title_sort |
claudins: beyond tight junctions in human ibd and murine models |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/08d266c4a2644bd6848be78913f1a5f4 |
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