Thrombospondin-1 type 1 repeats in a model of inflammatory bowel disease: transcript profile and therapeutic effects

Autor: Rebecca Stanton, Robert Terry, Michelle Wakeley, Anastasya Menaker, Sridar V. Chittur, Linda S. Gutierrez, Zenaida Lopez-Dee, Brittany Lippert, Bethany Eiche, Bhumi Patel
Rok vydání: 2011
Předmět:
Chemokine
Microarray
Mouse
lcsh:Medicine
Apoptosis
Inflammatory bowel disease
Transcriptome
Thrombospondin 1
Mice
0302 clinical medicine
Neoplasms
Molecular Cell Biology
Gastrointestinal Cancers
Leukocytes
lcsh:Science
0303 health sciences
Multidisciplinary
biology
Neovascularization
Pathologic
Stem Cells
Matricellular protein
Dextran Sulfate
Animal Models
Colitis
Recombinant Proteins
3. Good health
Up-Regulation
030220 oncology & carcinogenesis
Medicine
medicine.symptom
Veterinary Pathology
Research Article
Repetitive Sequences
Amino Acid
Drugs and Devices
Histology
Drug Research and Development
Colon
Immunology
Inflammation
Gastroenterology and Hepatology
Real-Time Polymerase Chain Reaction
03 medical and health sciences
Model Organisms
medicine
Cell Adhesion
Animals
RNA
Messenger
Biology
030304 developmental biology
lcsh:R
Inflammatory Bowel Disease
medicine.disease
Inflammatory Bowel Diseases
Molecular biology
Protein Structure
Tertiary
Disease Models
Animal
Pharmacogenetics
biology.protein
lcsh:Q
Veterinary Science
Zdroj: PLoS ONE
PLoS ONE, Vol 7, Iss 4, p e34590 (2012)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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