Tenascin-C is a driver of inflammation in the DSS model of colitis

Inflammatory Bowel Disease (IBD) is a grouping of chronic inflammatory disorders of the gut. Tenascin-C is a pro-inflammatory, extracellular matrix protein found upregulated in IBD patients and whilst a pathological driver of chronic inflammation, its precise role in the etiology of IBD is unknown....

Full description

Bibliographic Details
Main Authors: Ozanne, J, Shek, B, Stephen, LA, Novak, A, Milne, E, Mclachlan, G, Midwood, KS, Farquharson, C
Format: Journal article
Language:English
Published: Elsevier 2022
_version_ 1826308893823729664
author Ozanne, J
Shek, B
Stephen, LA
Novak, A
Milne, E
Mclachlan, G
Midwood, KS
Farquharson, C
author_facet Ozanne, J
Shek, B
Stephen, LA
Novak, A
Milne, E
Mclachlan, G
Midwood, KS
Farquharson, C
author_sort Ozanne, J
collection OXFORD
description Inflammatory Bowel Disease (IBD) is a grouping of chronic inflammatory disorders of the gut. Tenascin-C is a pro-inflammatory, extracellular matrix protein found upregulated in IBD patients and whilst a pathological driver of chronic inflammation, its precise role in the etiology of IBD is unknown. To study tenascin-C’s role in colitis pathology we investigated its expression in a murine model of IBD. Wild-type (WT) or tenascin-C knockout (KO) male mice were left untreated or treated with dextran sodium sulphate (DSS) in their drinking water. Tenascin-C was upregulated at the mRNA level in the colitic distal colon of day eight DSS treated mice, coinciding with significant increases in gross and histological pathology. Immunohistochemistry localized this increase in tenascin-C to areas of inflammation and ulceration in the mucosa. Tenascin-C KO mice exhibited reduced gross pathology in comparison. These differences also extended to the histopathological level where reduced colonic inflammation and tissue damage were found in KO compared to WT mice. Furthermore, the severity of the distal colon lesions were less in the KO mice after 17 days of recovery from DSS treatment. This study demonstrates a role for tenascin-C as a driver of inflammatory pathology in a murine model of IBD and thus suggests neutralizing its pro-inflammatory activity could be explored as a therapeutic strategy for treating IBD.
first_indexed 2024-03-07T07:27:44Z
format Journal article
id oxford-uuid:aa05f6a6-3271-4c84-b328-8910278679c4
institution University of Oxford
language English
last_indexed 2024-03-07T07:27:44Z
publishDate 2022
publisher Elsevier
record_format dspace
spelling oxford-uuid:aa05f6a6-3271-4c84-b328-8910278679c42022-11-24T11:13:02ZTenascin-C is a driver of inflammation in the DSS model of colitisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:aa05f6a6-3271-4c84-b328-8910278679c4EnglishSymplectic ElementsElsevier2022Ozanne, JShek, BStephen, LANovak, AMilne, EMclachlan, GMidwood, KSFarquharson, CInflammatory Bowel Disease (IBD) is a grouping of chronic inflammatory disorders of the gut. Tenascin-C is a pro-inflammatory, extracellular matrix protein found upregulated in IBD patients and whilst a pathological driver of chronic inflammation, its precise role in the etiology of IBD is unknown. To study tenascin-C’s role in colitis pathology we investigated its expression in a murine model of IBD. Wild-type (WT) or tenascin-C knockout (KO) male mice were left untreated or treated with dextran sodium sulphate (DSS) in their drinking water. Tenascin-C was upregulated at the mRNA level in the colitic distal colon of day eight DSS treated mice, coinciding with significant increases in gross and histological pathology. Immunohistochemistry localized this increase in tenascin-C to areas of inflammation and ulceration in the mucosa. Tenascin-C KO mice exhibited reduced gross pathology in comparison. These differences also extended to the histopathological level where reduced colonic inflammation and tissue damage were found in KO compared to WT mice. Furthermore, the severity of the distal colon lesions were less in the KO mice after 17 days of recovery from DSS treatment. This study demonstrates a role for tenascin-C as a driver of inflammatory pathology in a murine model of IBD and thus suggests neutralizing its pro-inflammatory activity could be explored as a therapeutic strategy for treating IBD.
spellingShingle Ozanne, J
Shek, B
Stephen, LA
Novak, A
Milne, E
Mclachlan, G
Midwood, KS
Farquharson, C
Tenascin-C is a driver of inflammation in the DSS model of colitis
title Tenascin-C is a driver of inflammation in the DSS model of colitis
title_full Tenascin-C is a driver of inflammation in the DSS model of colitis
title_fullStr Tenascin-C is a driver of inflammation in the DSS model of colitis
title_full_unstemmed Tenascin-C is a driver of inflammation in the DSS model of colitis
title_short Tenascin-C is a driver of inflammation in the DSS model of colitis
title_sort tenascin c is a driver of inflammation in the dss model of colitis
work_keys_str_mv AT ozannej tenascincisadriverofinflammationinthedssmodelofcolitis
AT shekb tenascincisadriverofinflammationinthedssmodelofcolitis
AT stephenla tenascincisadriverofinflammationinthedssmodelofcolitis
AT novaka tenascincisadriverofinflammationinthedssmodelofcolitis
AT milnee tenascincisadriverofinflammationinthedssmodelofcolitis
AT mclachlang tenascincisadriverofinflammationinthedssmodelofcolitis
AT midwoodks tenascincisadriverofinflammationinthedssmodelofcolitis
AT farquharsonc tenascincisadriverofinflammationinthedssmodelofcolitis