Abstract
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.