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1.  Thrombospondin-1 Type 1 Repeats in a Model of Inflammatory Bowel Disease: Transcript Profile and Therapeutic Effects 
PLoS ONE  2012;7(4):e34590.
Thrombospondin-1 (TSP-1) is a matricellular protein with regulatory functions in inflammation and cancer. The type 1 repeats (TSR) domains of TSP-1 have been shown to interact with a wide range of proteins that result in the anti-angiogenic and anti-tumor properties of TSP-1. To ascertain possible functions and evaluate potential therapeutic effects of TSRs in inflammatory bowel disease, we conducted clinical, histological and microarray analyses on a mouse model of induced colitis. We used dextran sulfate sodium (DSS) to induce colitis in wild-type (WT) mice for 7 days. Simultaneously, mice were injected with either saline or one form of TSP-1 derived recombinant proteins, containing either (1) the three type 1 repeats of the TSP-1 (3TSR), (2) the second type 1 repeat (TSR2), or (3) TSR2 with the RFK sequence (TSR2+RFK). Total RNA isolated from the mice colons were processed and hybridized to mouse arrays. Array data were validated by real-time qPCR and immunohistochemistry. Histological and disease indices reveal that the mice treated with the TSRs show different patterns of leukocytic infiltration and that 3TSR treatment was the most effective in decreasing inflammation in DSS-induced colitis. Transcriptional profiling revealed differentially expressed (DE) genes, with the 3TSR-treated mice showing the least deviation from the WT-water controls. In conclusion, this study shows that 3TSR treatment is effective in attenuating the inflammatory response to DSS injury. In addition, the transcriptomics work unveils novel genetic data that suggest beneficial application of the TSR domains in inflammatory bowel disease.
doi:10.1371/journal.pone.0034590
PMCID: PMC3318003  PMID: 22509329
2.  Thrombospondin-1: Multiple Paths to Inflammation 
Mediators of Inflammation  2011;2011:296069.
Inflammation is a defensive process against tissue injury. Once this self-protective strategy is initiated, an effective resolution of the process is crucial to avoid major and unnecessary tissue damage. If the underlying event inducing inflammation is not addressed and homeostasis is not restored, this process can become chronic and lead to angiogenesis and carcinogenesis. Thrombospondin-1 (TSP-1) is a matricellular protein involved in angiogenesis, cancer, and inflammation. The effects of TSP-1 have been studied in many preclinical tumor models, and mimetic peptides are being tested in cancer clinical trials. However, the molecular mechanisms explaining its role in inflammatory processes are not well understood. This paper will discuss the role of TSP-1 in inflammation and its interaction with key receptors that may explain its functions in that process. Recent literature will be reviewed showing novel mechanisms by which this multifaceted protein could modulate the inflammatory process and impact its resolution.
doi:10.1155/2011/296069
PMCID: PMC3134184  PMID: 21765615
3.  The Role of Thrombospondin 1 on Intestinal Inflammation and Carcinogenesis 
Biomarker insights  2008;3:171-178.
Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBD) quite common in the United States and other Western countries. Patients suffering IBD are at greater risk of developing colorectal adenocarcinoma than the general population. Both, the adenoma-carcinoma and the inflammation-carcinogenesis processes are characterized by active angiogenesis. Recent studies also have shown that anti-angiogenesis might be a novel therapeutic approach for IBD. Thrombospondin 1 (TSP1) is an extracellular protein well known for its anti-angiogenic properties. TSP1 also has key functions in inflammation, which is assumed to be the primary cause for carcinogenesis in IBD. This review is focused on the role of TSP1 in colorectal carcinogenesis. The therapeutic effects of TSP derived-peptides on inhibiting the inflammationcarcinogenesis progression are also discussed.
PMCID: PMC2600574  PMID: 19079771
transforming growth factor beta 1; angiogenesis; ApcMin + mouse; CD36; inflammatory bowel disease
4.  The Role of Thrombospondin 1 on Intestinal Inflammation and Carcinogenesis 
Biomarker Insights  2008;3:171-178.
Crohn’s disease and ulcerative colitis are inflammatory bowel diseases (IBD) quite common in the United States and other Western countries. Patients suffering IBD are at greater risk of developing colorectal adenocarcinoma than the general population. Both, the adenomacarcinoma and the inflammation-carcinogenesis processes are characterized by active angiogenesis. Recent studies also have shown that anti-angiogenesis might be a novel therapeutic approach for IBD. Thrombospondin 1 (TSP1) is an extracellular protein well known for its anti-angiogenic properties. TSP1 also has key functions in inflammation, which is assumed to be the primary cause for carcinogenesis in IBD. This review is focused on the role of TSP1 in colorectal carcinogenesis. The therapeutic effects of TSP derived-peptides on inhibiting the inflammation-carcinogenesis progression are also discussed.
PMCID: PMC2600574  PMID: 19079771
transforming growth factor beta 1; angiogenesis; ApcMin + mouse; CD36; inflammatory bowel disease

Results 1-4 (4)