Thrombospondin-1 Type 1 Repeats in a Model of Inflammatory Bowel Disease: Transcript Profile and Therapeutic EffectsReportar como inadecuado




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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.



Autor: Zenaida P. Lopez-Dee, Sridar V. Chittur, Bhumi Patel, Rebecca Stanton, Michelle Wakeley, Brittany Lippert, Anastasya Menaker, Bet

Fuente: http://plos.srce.hr/



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