炎症性肠病
炎症
髓过氧化物酶
血管生成
川地31
偶氮甲烷
结肠炎
内科学
新生血管
医学
体内
肿瘤坏死因子α
内分泌学
免疫学
化学
结直肠癌
生物
癌症
疾病
生物技术
作者
Salman R Punekar,Samantha Zak,Valerie G. Kalter,Larissa Dobransky,Imran Punekar,Jack Lawler,Linda S. Gutierrez
出处
期刊:Pathobiology
[S. Karger AG]
日期:2008-01-01
卷期号:75 (1): 9-21
被引量:56
摘要
<i>Objective:</i> Vascular abnormalities and expression of proangiogenic factors have been repeatedly reported in inflammatory bowel disease (IBD). Thrombospondin 1 (TSP-1) is a protein well known for its antiangiogenic and anti-inflammatory properties. Using the dextran sulfate sodium (DSS) model, the role of TSP-1 in IBD has been investigated in vivo. <i>Methods:</i> TSP-1-deficient mice (TSP-1<sup>–/–</sup>) and WT mice were treated with DSS for 7 days. Disease activity indices, myeloperoxidase activity (MPO) and histology were analyzed. Microvascular density (MVD) was quantified using immunohistochemistry (IMH) with CD31 antibody. TGF-β<sub>1</sub>, basic FGF, VEGF, TNF-α and MMPs protein levels were evaluated by IMH and enzyme-linked immunoabsorbent assay (ELISA). Mice were treated with ABT-510 (Abbott Laboratories), an antiangiogenic TSP peptide, using miniosmotic pumps for 7 days. <i>Results:</i> TSP-1<sup>–/–</sup> mice had a worse clinical outcome and exhibited severe signs of rectal bleeding compared to the WT controls. The TSP-1<sup>–/–</sup> mice showed a higher level of crypt damage and deeper lesions. The grade of inflammation and the levels of MPO activity were also significantly higher in colons of TSP-1<sup>–/–</sup> mice. TSP-1<sup>–/–</sup> mice displayed higher MVD in focal areas of the colon after only 3 days of DSS treatment. Furthermore, clinical severity of the colitis and angiogenesis was significantly diminished when mice was treated with ABT-510. <i>Conclusions:</i> These findings directly link TSP-1 as a protective factor in IBD and suggest antiangiogenesis treatment, including compounds such as ABT-510 as an adjuvant therapy for IBD.
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