Activated Syndecan-1 Shedding Contributes to Mice Colitis Induced by Dextran Sulfate Sodium
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Xia Wang Ye Chen Yugang Song Shaoheng Zhang Xiaoyun Xie Xianfei Wang
- چاپ و سال / کشور: 2010
Description
Background Syndecan-1(Sdc1) plays important roles in many steps of inflammatory responses. In ulcerative colitis patients, decreased Sdc1 expression was observed and Sdc1 analogue heparin could improve the disease course. A better understanding of how Sdc1 functions in colitis will benefit the disease intervention. Aims To evaluate the role of Sdc1 in dextran sulfate sodium (DSS)-induced colitis. Methods BALB/c mice were grouped randomly into control, DSS, and heparin?DSS. The DSS group was given 4% DSS orally and heparin?DSS group was given 4% DSS with heparin (enoxaparin) subcutaneously, while the control was given distilled water orally. All mice were killed at day 7. Disease activities, histopathological changes, membrane-bound and free Sdc1 level and mRNA expression of Sdc1, IL-1, and IL-10 in colon mucosa were detected. Results Significant colitis was observed in the DSS group, but disease activity index and histological score showed significant lower in the heparin?DSS group than those in the DSS group. Compared to the control group, decreased Sdc1 protein expression was detected in colon mucosa of DSS-induced colitis while Sdc1 ectodomain level in serum was much higher. Inhibited Sdc1 ectodomain shedding was detected in the heparin?DSS group compared to the DSS group. RT-PCR demonstrated that both IL-1 and IL-10 expression were up-regulated in DSS-induced colitis while heparin lessened the up-regulation extent. Conclusions Sdc1 shedding is activated in DSS-induced colitis and heparin, which mimics Sdc1 functions, relieves colitis severity by inhibiting Sdc1 shedding and downregulating cytokines expression.
Dig Dis Sci (2011) 56:1047–1056 DOI 10.1007/s10620-010-1398-8 Received: 27 February 2010 / Accepted: 12 August 2010 / Published online: 9 October 2010
