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08.23 Syndecan-4 exerts a protective function in experimental intestinal inflammation
  1. Mareike Fröhling1,
  2. Dominik Bettenworth2,
  3. Sonja Dufentester2,
  4. Peter Paruzel1,
  5. Frank Echtermeyer3,
  6. Andreas Lügering2,4,
  7. Thomas Pap1,
  8. Athanasios Stratis1
  1. 1Institut of Experimental Musculoskeletal Medicine, University Muenster, Muenster, Germany
  2. 2Department of Medicine B, University Muenster, Muenster, Germany
  3. 3Department of Anesthesiology and Intensive Care Medicine, Medical University Hannover, Hannover, Germany
  4. 4MVZ Portal 10, Muenster, Germany

Abstract

Background The ubiquitously expressed transmembrane heparan sulfate proteoglycan Syndecan-4 (Scd4) is crucial in inflammatory diseases, like rheumatoid arthritis. Depending on the tissue, it can either protect or promote an inflammatory process. By its binding of molecules, such as cytokines and growth factors, it can initiate signalling pathways and it has been implicated in cell-matrix adhesion, cell migration, differentiation as well as proliferation. However, the involvement of Sdc4 in intestinal inflammation is unknown so far. Our group revealed a protective function of Sdc4 in experimental intestinal inflammation.

Material and methods We monitored the course of DSS-induced colitis in Scd4-/- and C57BL/6 WT mice and analysed the changes in body weight, colon length, histology and inflammatory cellular infiltrate. We also evaluated Sdc4 protein- and mRNA-level by immunofluorescence staining (IF) and quantitative real-time PCR. Colon-permeability was examined in vivo by using the Evans Blue method and measuring the clearance for Citrobacter rodentium in vivo. Wound healing effects of Scd4 were analysed in vitro by scratch assay analysis with human epithelial colon cell line (T-84) and in vivo by mechanically induced wounds in colonoscopies of Scd4-/- compared to WT mice.

Results The expression of Scd4 is decreased upon the course of colitis and increased during remission. The course of colitis was markedly aggravated in Scd4-/- mice, reflected by dramatically loss of body weight, increased mortality rates and histological damage, emphasised by increased invasion of macrophages and granulocytes into the colon. Also colonic epithelial permeability of DSS-treated Scd4-/- mice was enhanced associated with an altered expression of tight junction proteins. Furthermore, Sdc4 deficiency resulted in a prolonged intestinal wound healing in vitro and in vivo due to reduced proliferation rates in vitro.

Conclusions Our data indicates that Scd4 is crucial in experimental intestinal inflammation. It exerts protective effects by maintaining epithelial barrier integrity and regeneration. Further studies are needed to explore the mechanisms of Sdc4-signalling in colitis.

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