- Thrombospondin 1
- Inflammatory bowel disease
- Metalloproteinase 2
- Basic FGF
Objective: 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. Methods: TSP-1-deficient mice (TSP-1–/–) 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-β1, 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. Results: TSP-1–/– mice had a worse clinical outcome and exhibited severe signs of rectal bleeding compared to the WT controls. The TSP-1–/– 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–/– mice. TSP-1–/– 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. Conclusions: 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.
Copyright © 2008 S. Karger AG, Basel
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Dr. Linda S. Gutierrez
Department of Biology, 354 Stark Learning Center
Wilkes University, 84 W. South St.
Wilkes-Barre, PA 18766 (USA)
Tel. +1 570 408 4636, Fax +1 570 408 7862, E-Mail firstname.lastname@example.org
Received: June 12, 2007
Accepted: September 7, 2007
Published online: March 11, 2008
Number of Print Pages : 13
Number of Figures : 6, Number of Tables : 0, Number of References : 42
Pathobiology (Pathobiology - Exploring the basis of disease)
Vol. 75, No. 1, Year 2008 (Cover Date: March 2008)
Journal Editor: Borisch B. (Geneva), Yasui W. (Hiroshima)
ISSN: 1015–2008 (Print), eISSN: 1423–0291 (Online)
For additional information: http://www.karger.com/PAT
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