Background and Objectives The transmembrane heparan sulphate proteoglycan syndecan-4 (Scd4) has been implicated in cell-matrix adhesion, cell migration, differentiation, proliferation and plays an important role during inflammation in rheumatoid arthritis. Scd4 is a mediator and modulator of inflammatory signals, upon its binding of cytokines Scd4 acts either as a decoy receptor or through the initiation of Scd-dependend signalling, followed by the formation of a Scd4 complex. Cartilage damage is decreased in sdc4-deficient mice, but osteopontin-mediated liver damage is increased. Because of these dual effects we investigate the impact of sdc4 in murine experimental colitis.
Materials and Methods We performed DSS-induced colitis in Scd4-/- and C57BL/6 WT mice. We used weight loss, colon length and histological scoring of colonic modifications to measure the course of colitis. Scd4-/- and WT mice were orally gavaged with 5 × 108 colony-forming units (CFU) of invasive bacterium Citrobacter rhodentium (C. rhodentium). The changes of body weight and faecal excretion of C. rhodentium were monitored for 21 days followed by evaluation of histological changes after infection. The permeability of the colon was examined in vitro by infection of colon samples from Scd4-/- and C57BL/6 WT mice with C. rhodentium. The migration behaviour of endothelial human cells (T-84) and scd4-siRNA T-84 knockdown cells was analysed by scratch assay.
Results DSS-treated Scd4-/- mice lost dramatically more body weight compared to the WT mice and the histological damage according to the Dieleman-Score was markedly increased. At day 19 of post infection the clearance of C. rhodentium in Scd4-/- mice was markedly prolonged. In vitro infection of colon samples from Scd4-/- mice with C. rhodentium revealed a higher permeability for the bacterium compared to WT colon samples. The knockdown of Scd4 in human endothelial T-84 cells leads to delayed cell migration.
Conclusions Like in inflammatory liver damage, Scd4 appears to play an important role in colitis and exerts protective effects in intestinal inflammation. The Scd4 deficiency leads to a higher permeability of the colon to C. rhodentium and a delayed cell migration. Further analysis are needed to explore the mechanisms of Sdc4-signalling in colitis.
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