The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: implications for epithelial protection
| Autor: | Ingrid B. Renes, Johannes B. van Goudoever, Audrey Vincent, Maria van der Sluis, Nanda Burger-van Paassen, Günther Boehm, Patrycja J. Puiman, Janneke Bouma, Isabelle Van Seuningen |
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| Přispěvatelé: | General Paediatrics, Laboratory of Pediatrics, Division of Neonatology, Erasmus Medical Centre-Sophia children's hospital, Pediatrics |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Chromatin Immunoprecipitation
Proto-Oncogene Proteins c-jun Blotting Western Electrophoretic Mobility Shift Assay Butyrate Biology Response Elements Biochemistry digestive system Histones 03 medical and health sciences Histone H3 0302 clinical medicine Cell Line Tumor Histone methylation Gene expression Humans RNA Messenger Promoter Regions Genetic Molecular Biology 030304 developmental biology Cell Proliferation chemistry.chemical_classification 0303 health sciences Messenger RNA Mucin-2 Binding Sites Base Sequence Dose-Response Relationship Drug Reverse Transcriptase Polymerase Chain Reaction Short-chain fatty acid Life Sciences Acetylation Epithelial Cells Cell Biology respiratory system Molecular biology Immunohistochemistry digestive system diseases Transcription Factor AP-1 Butyrates chemistry Gene Expression Regulation 030220 oncology & carcinogenesis Mutation Propionate Chromatin immunoprecipitation Proto-Oncogene Proteins c-fos Protein Binding |
| Zdroj: | Biochemical journal, 420(2), 211-219. Portland Press Ltd. Biochemical Journal Biochemical Journal, Portland Press, 2009, 420 (2), pp.211-219. ⟨10.1042/BJ20082222⟩ ResearcherID Biochemical Journal, 420, 211-219. Portland Press, Ltd. |
| ISSN: | 0264-6021 1470-8728 |
| DOI: | 10.1042/BJ20082222⟩ |
| Popis: | SCFAs (short-chain fatty acids), fermentation products of bacteria, influence epithelial-specific gene expression. We hypothesize that SCFAs affect goblet-cell-specific mucin MUC2 expression and thereby alter epithelial protection. In the present study, our aim was to investigate the mechanisms that regulate butyrate-mediated effects on MUC2 synthesis. Human goblet cell-like LS174T cells were treated with SCFAs, after which MUC2 mRNA levels and stability, and MUC2 protein expression were analysed. SCFA-responsive regions and cis-elements within the MUC2 promoter were identified by transfection and gel-shift assays. The effects of butyrate on histone H3/H4 status at the MUC2 promoter were established by chromatin immunoprecipitation. Butyrate (at 1 mM), as well as propionate, induced an increase in MUC2 mRNA levels. MUC2 mRNA levels returned to basal levels after incubation with 5–15 mM butyrate. Interestingly, this decrease was not due to loss of RNA stability. In contrast, at concentrations of 5–15 mM propionate, MUC2 mRNA levels remained increased. Promoter-regulation studies revealed an active butyrate-responsive region at −947/−371 within the MUC2 promoter. In this region we identified an active AP1 (c-Fos/c-Jun) cis-element at −818/−808 that mediates butyrate-induced activation of the promoter. Finally, MUC2 regulation by butyrate at 10–15 mM was associated with increased acetylation of histone H3 and H4 and methylation of H3 at the MUC2 promoter. In conclusion, 1 mM butyrate and 1–15 mM propionate increase MUC2 expression. The effects of butyrate on MUC2 mRNA are mediated via AP-1 and acetylation/methylation of histones at the MUC2 promoter. |
| Databáze: | OpenAIRE |
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