Soluble Syndecan-1 Levels Are Elevated in Patients with Inflammatory Bowel Disease

Yablecovitch, Doron; Stein, Assaf; Shabat-Simon, Maytal; Naftali, Timna; Gabay, Gila; Laish, Ido; Oren, Asaf; Konikoff, Fred M.

doi:10.1007/s10620-015-3589-9

Cited by 23 publications

(24 citation statements)

References 37 publications

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“…These above results are consistent with those found in patients with Crohn's disease (CD), which demonstrated the decreased levels of SDC1 in the intestinal mucosa and the increased levels of its ectodomain in the serum . However, our results are different from a recent study performed by Israeli researchers, which showed elevated levels of soluble SDC‐1 in CD patients, but no difference between UC patients and healthy controls . The causes of the differentiated outcomes between Israeli patients and our study were unknown yet.…”

Section: Discussioncontrasting

confidence: 99%

Cell surface‐anchored syndecan‐1 ameliorates intestinal inflammation and neutrophil transmigration in ulcerative colitis

Zhang

Wang

et al. 2016

J Cellular Molecular Medi

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Syndecan‐1 (SDC1), with a variable ectodomain carrying heparan sulphate (HS) chains between different Syndecans, participates in many steps of inflammatory responses. In the process of proteolysis, the HS chains of the complete extracellular domain can be shed from the cell surface, by which they can mediate most of SDC1's function. However, the exact impact on SDC1 which anchored on the cell surface has not been clearly reported. In our study, we established the models by transfection with the cleavable resistant SDC1 mutant plasmid, in which SDC1 shedding can be suppressed during stimulation. Role of membrane SDC1 in inflammatory pathway, pro‐inflammatory cytokine secretion as well as neutrophil transmigration, and how suppressing its shedding will benefit colitis were further investigated. We found that the patients suffered ulcerative colitis had high serum SDC1 levels,presented with increased levels of P65, tumour necrosis factor alpha (TNF‐α) and IL‐1β and higher circulating neutrophils. NF‐κB pathway was activated, and secretion of TNF‐α, interleukin‐1beta (IL‐1β), IL‐6 and IL‐8 were increased upon lipopolysaccharide stimuli in intestinal epithelial cells. Syndecan‐1, via its anchored ectodomain, significantly lessened these up‐regulation extents. It also functioned in inhibiting transmigration of neutrophils by decreasing CXCL‐1 secretion. Moreover, SDC1 ameliorated colitis activity and improved histological disturbances of colon in mice. Taken together, we conclude that suppression of SDC1 shedding from intestinal epithelial cells relieves severity of intestinal inflammation and neutrophil transmigration by inactivating key inflammatory regulators NF‐κB, and down‐regulating pro‐inflammatory cytokine expressions. These indicated that compenstion and shedding suppression of cytomembrane SDC1 might be the optional therapy for intestinal inflammation.

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Section: Discussioncontrasting

confidence: 99%

Cell surface‐anchored syndecan‐1 ameliorates intestinal inflammation and neutrophil transmigration in ulcerative colitis

Zhang

Wang

et al. 2016

J Cellular Molecular Medi

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“…(13) Clinical studies in patients with inflammatory bowel disease have shown that Crohns patients had significantly reduced intestinal syndecan-1 that correlated with disease severity. (17) Yablecovitch et al demonstrated elevated levels of soluble syndecan-1 in serum of patients with both Crohn's and ulcerative colitis. (18) These studies highlight the important and newly appreciated role of syndecan-1 in intestinal pathology.…”

Section: Discussionmentioning

confidence: 99%

Plasma-Mediated Gut Protection After Hemorrhagic Shock is Lessened in Syndecan-1−/− MICE

Ban

Peng

Pati

et al. 2015

Shock

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We have shown in a rodent model of hemorrhagic shock (HS) that fresh frozen plasma (FFP) reduces lung inflammation and injury which are correlated with restitution of syndecan-1. Since the gut is believed to contribute to distant organ injury and inflammation after shock, the current study sought to determine if the protective effects of plasma would extend to the gut and to elucidate the contribution of syndecan-1 to this protective effect. We also examined the potential role of TNFα, and a disintegrin and metalloproteinase (ADAM)-17, both intestinal sheddases of syndecan-1. Wild-type (WT) and syndecan-1−/− (KO) mice were subjected to HS followed by resuscitation with lactated ringers (LR) or FFP and compared to shock alone and shams. Small bowel and blood were obtained after 3 hours for analysis of mucosal injury and inflammation and TNFα and ADAM-17 protein expression and activity. After HS, gut injury and inflammation were significantly increased compared to shams. Resuscitation with LR decreased both injury and inflammation which were further lessened by FFP. KO mice displayed worsened gut injury and inflammation after HS compared to WT mice, and LR and FFP equivalently inhibited injury and inflammation. Both systemic and intestinal TNFα and ADAM-17 followed similar trends, with increases after HS, reduction by LR, and a further decrease by FFP in WT but not KO mice. In conclusion, FFP decreased gut injury and inflammation after hemorrhagic shock, an effect that was abrogated in syndecan-1−/− mice. Plasma also decreased TNFα and ADAM-17, representing a potential mechanistic link to its protection via syndecan-1.

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“…On the other hand, IBD patients had higher soluble SDC-1 levels compared to healthy controls in the research by Yablecovitch et al However, in the same study, no correlation was found in SDC-1 between CRP and disease activity in contrast to our study. The reason for this difference may be attributed to the presence of large group of UC patients which has no significant difference in SDC-1 levels with the healthy controls in the subgroup analysis [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Serum Syndecan-1 Levels and Its Relationship to Disease Activity in Patients with Crohn’s Disease

Çekiç

Kirci

Vatansever

et al. 2015

Gastroenterology Research and Practice

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Background. Syndecan-1 (SDC-1), a member of the family of heparan sulfate proteoglycans, plays an important role in the resolution of inflammation. This study aimed to investigate the relationship between SDC-1 and disease activity in Crohn's disease (CD). Methods. Serum samples of 54 patients with CD and 30 healthy controls were obtained. First, SDC-1 levels of the CD patients were compared to the control group. Subsequently, SDC-1 levels were analyzed in patients with CD in active and remission periods. Finally, SDC-1 efficacy in predicting disease activity was evaluated by performing correlation analysis between SDC-1 and C-reactive protein (CRP) and Crohn's disease activity index (CDAI). Results. SDC-1 level was higher in the CD group (61.9 ± 42.6 ng/mL) compared with the control group (34.1 ± 8.0 ng/mL) (p = 0.03). SDC-1 levels were higher in active CD patients (97.1 ± 40.3 ng/mL) compared with those in remission (33.7 ± 13.5 ng/mL) (p < 0.001). A significant positive correlation was found between SDC-1 and CRP (r = 0.687, p < 0.001) and between SDC-1 and CDAI (r = 0.747, p < 0.001). Conclusion. Serum levels of SDC-1 are higher in CD compared to the normal population and can be an effective marker of disease severity.

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Soluble Syndecan-1 Levels Are Elevated in Patients with Inflammatory Bowel Disease

Abstract: Our results suggest that soluble syndecan-1 is potentially a novel diagnostic marker in the management of inflammatory bowel disease patients. Its applicability as a surrogate, prognostic biomarker remains to be determined.

Cited by 23 publications

References 37 publications

Cell surface‐anchored syndecan‐1 ameliorates intestinal inflammation and neutrophil transmigration in ulcerative colitis

Cell surface‐anchored syndecan‐1 ameliorates intestinal inflammation and neutrophil transmigration in ulcerative colitis

Plasma-Mediated Gut Protection After Hemorrhagic Shock is Lessened in Syndecan-1−/− MICE

Serum Syndecan-1 Levels and Its Relationship to Disease Activity in Patients with Crohn’s Disease

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