Enoxaparin improves the course of dextran sodium sulfate-induced colitis in syndecan-1-deficient mice.
Floer M, Götte M, Wild MK, Heidemann J, Gassar ES, Domschke W, Kiesel L, Luegering A, Kucharzik T
Research article (journal)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.
Details about the publication
Authors from the University of Münster
| Floer, Werner Martin | Medical Clinic of Internal Medicine B: Gastroenterology and Metabolic Disorders (Med B) |
| Götte, Martin | Department of Gynecology and Obstetrics |
| Heidemann, Jan | Medical Clinic of Internal Medicine B: Gastroenterology and Metabolic Disorders (Med B) |
| Kiesel, Ludwig | Department of Gynecology and Obstetrics |
Projects the publication originates from
Duration: 01/01/2010 - 31/12/2012 Funded by: German-Israeli Foundation for Scientific Research and Development Type of project: Individual project | |
Duration: 01/01/2010 - 31/12/2010 | 1st Funding period Funded by: DFG - Initiation of International Collaboration Type of project: Individual project |
Promotionen, aus denen die Publikation resultiert
| Role of the heparan sulfate sulfotransferase HS3ST2 in breast cancer cell motility and invasiveness Candidate: Gassar, Ezeddin Salem | Supervisors: Götte, Martin; Stock, Christian; Kiesel, Ludwig Period of time: until 01/04/2011 Doctoral examination procedure finished at: Doctoral examination procedure at University of Münster |
Habilitationen, aus denen die Publikation resultiert
Role of the heparan sulfate proteoglycan Syndecan-1 as a modulator of inflammation and tumor progression Candidate: Götte, Martin | Reviewers: Kiesel, LudwigPeriod of time: 01/01/2008 - 12/04/2011 Habilitation procedure finished at: Habilitation procedure at University of Münster |