Dietary black raspberries modulate DNA methylation in dextran sodium sulfate (DSS)-induced ulcerative colitis
| Autor: | Kristen Stoner, Yi-Wen Huang, Martha Yearsley, Chieh Ti Kuo, Dan Peiffer, Li-Shu Wang, Daniel W. Rosenberg, Tim H M Huang, Kiyoko Oshima, Jianhua Yu, Gary D. Stoner |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Cancer Research Methyltransferase Colon Histone Deacetylase 2 Original Manuscript Histone Deacetylase 1 Spleen Inflammation Biology Proinflammatory cytokine Mice Proto-Oncogene Proteins c-myb Bone Marrow medicine Animals DNA (Cytosine-5-)-Methyltransferases RNA Messenger Promoter Regions Genetic Wnt Signaling Pathway Adaptor Proteins Signal Transducing Dextran Sulfate Wnt signaling pathway General Medicine DNA Methylation medicine.disease Ulcerative colitis digestive system diseases DNA-Binding Proteins Mice Inbred C57BL medicine.anatomical_structure Fruit DNA methylation Immunology Cancer research Intercellular Signaling Peptides and Proteins Colitis Ulcerative Bone marrow medicine.symptom |
| Zdroj: | Carcinogenesis. 34:2842-2850 |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/bgt310 |
| Popis: | Ulcerative colitis (UC) is characterized by chronic inflammation of the colon. During inflammation, NF-κB is increased in colonic epithelial cells and in immune cells, leading to increases in proinflammatory cytokines. These events then increase DNA methyltransferases (DNMTs), which silence a subset of tumor suppressor genes by promoter methylation. Negative regulators of the Wnt pathway are frequently methylated in UC, leading to dysregulation of the pathway and, potentially, to colorectal cancer. We determined if black raspberries (BRBs) influence promoter methylation of suppressors in the Wnt pathway in dextran sodium sulfate (DSS)-induced UC. C57BL/6J mice received 1% DSS and were fed either control or 5% BRB diets. Mice were euthanized on days 7, 14 and 28, and their colons, spleen and bone marrow were collected. Berries reduced ulceration at day 28. This was accompanied by decreased staining of macrophages and neutrophils and decreased NF-κB p65 nuclear localization in the colon at all time points. At day 7, BRBs demethylated the promoter of dkk3, leading to its increased messenger RNA (mRNA) expression in colon, spleen and bone marrow. β-Catenin nuclear localization, c-Myc staining as well as protein expression of DNMT3B, histone deacetylases 1 and 2 (HDAC1 and HDAC2) and methyl-binding domain 2 (MBD2) were all decreased in colon; mRNA expression of these four proteins was decreased in bone marrow cells by BRBs. These results suggest that BRBs suppress colonic ulceration by correcting promoter hypermethylation of suppressor genes in the colon, as well as in the spleen and bone marrow that systematically regulate inflammation. Summary: Our results suggest that dietary BRBs suppress colonic ulceration by correcting promoter hypermethylation of suppressor genes in the colon, as well as in the spleen and bone marrow that systematically regulate inflammation in DSS-induced UC. |
| Databáze: | OpenAIRE |
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