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Updated: Jun 17, 2026
Murine Colitis Modeling using Dextran Sulfate Sodium (DSS)
Published on: January 19, 2010
Enoxaparin improves the course of dextran sodium sulfate-induced colitis in syndecan-1-deficient mice
Martin Floer1, Martin Götte, Martin K Wild
1Department of Medicine B, Albert Schweitzer Strasse 33, D-48149 Muenster, Germany. martinfloer@web.de
Abstract:
Syndecan-1 (Sdc1) plays a major role in wound healing and modulates inflammatory responses. Sdc1 expression is reduced in lesions of patients with ulcerative colitis. The aim of this study was to investigate the role of Sdc1 in murine dextran sodium sulfate (DSS)-induced colitis. DSS colitis was induced in Sdc1-deficient (knockout (KO)) and wild-type mice by oral administration of 3% DSS. KO mice exhibited a significantly increased lethality as compared with wild-type controls (61 versus 5%, P < 0.05). Impaired mucosal healing and prolonged recruitment of inflammatory cells in KO mice were accompanied by significant up-regulation of tumor necrosis factor-alpha, CC chemokine ligand 3/macrophage inflammatory protein-1alpha, and vascular cell adhesion molecule-1, as determined by histological correlation between 0 and 15 days after colitis induction, TaqMan low-density array analysis, and quantitative real-time PCR. Treatment from days 7 through 14 with enoxaparin, a functional analogue of the Sdc1 heparan sulfate chains, significantly reduced lethality of KO mice due to DSS-induced colitis, which was correlated with improved mucosal healing. In vitro, Sdc1-deficient polymorphonuclear cells displayed increased adhesion to endothelial cells and intercellular adhesion molecule-1, and enoxaparin reverted adhesion to wild-type levels. Small interfering RNA-mediated knockdown of Sdc1 expression resulted in reduced basic fibroblast growth factor-mediated mitogen-activated protein kinase signaling and reduced Caco-2 cell proliferation. We conclude that Sdc1 has a protective effect during experimental colitis. The modification of missing Sdc1 function by heparin analogues may emerge as a promising anti-inflammatory approach.
Insights
Syndecan-1 (Sdc1) deficiency worsens experimental colitis, increasing mortality and impairing healing. Heparin analogues restored Sdc1 function, offering a potential anti-inflammatory therapy for colitis.
Area of Science:
- Immunology
- Gastroenterology
- Cell Biology
Background:
- Syndecan-1 (Sdc1) is crucial for wound healing and inflammation modulation.
- Reduced Sdc1 expression is observed in ulcerative colitis lesions.
- The role of Sdc1 in experimental colitis remains unclear.
Purpose of the Study:
- To investigate the function of Sdc1 in dextran sodium sulfate (DSS)-induced colitis in mice.
- To evaluate the therapeutic potential of Sdc1 functional analogues in colitis.
Main Methods:
- Induction of DSS colitis in Sdc1-deficient (KO) and wild-type mice.
- Assessment of lethality, mucosal healing, and inflammatory cell recruitment.
- Analysis of inflammatory markers using histology, TaqMan low-density array, and quantitative real-time PCR.
- In vitro studies on polymorphonuclear cell adhesion and Caco-2 cell proliferation.
- Treatment with enoxaparin, a heparin analogue.
Main Results:
- Sdc1 KO mice showed significantly increased lethality (61% vs 5%) and impaired mucosal healing compared to wild-type controls.
- KO mice exhibited elevated levels of TNF-α, CXCL1/MIP-1α, and ICAM-1.
- Enoxaparin treatment significantly reduced lethality and improved mucosal healing in KO mice.
- In vitro, Sdc1 deficiency increased polymorphonuclear cell adhesion, which was reversed by enoxaparin.
- Sdc1 knockdown reduced FGF-mediated signaling and Caco-2 cell proliferation.
Conclusions:
- Sdc1 exerts a protective role in experimental colitis.
- Heparin analogues represent a promising anti-inflammatory strategy for colitis by mimicking Sdc1 function.
