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.
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Research Article|
May 13 2009
The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: implications for epithelial protection
Nanda Burger-van Paassen;
Nanda Burger-van Paassen
1
*Department of Pediatrics, Division of Neonatology, Erasmus MC-Sophia, Rotterdam, 3015 GE, The Netherlands
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Audrey Vincent;
Audrey Vincent
1
†Inserm, U837, Centre de Recherche Jean-Pierre Aubert, Lille 59045, France
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Patrycja J. Puiman;
Patrycja J. Puiman
*Department of Pediatrics, Division of Neonatology, Erasmus MC-Sophia, Rotterdam, 3015 GE, The Netherlands
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Maria van der Sluis;
Maria van der Sluis
*Department of Pediatrics, Division of Neonatology, Erasmus MC-Sophia, Rotterdam, 3015 GE, The Netherlands
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Janneke Bouma;
Janneke Bouma
*Department of Pediatrics, Division of Neonatology, Erasmus MC-Sophia, Rotterdam, 3015 GE, The Netherlands
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Günther Boehm;
Günther Boehm
*Department of Pediatrics, Division of Neonatology, Erasmus MC-Sophia, Rotterdam, 3015 GE, The Netherlands
‡Danone Research Centre for Specialised Nutrition, Friedrichsdorf 61381, Germany
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Johannes B. van Goudoever;
Johannes B. van Goudoever
*Department of Pediatrics, Division of Neonatology, Erasmus MC-Sophia, Rotterdam, 3015 GE, The Netherlands
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Isabelle van Seuningen;
Isabelle van Seuningen
2
†Inserm, U837, Centre de Recherche Jean-Pierre Aubert, Lille 59045, France
2Correspondence may be addressed to either of these authors (email isabelle.vanseuningen@inserm.fr or i.renes@erasmusmc.nl).
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Ingrid B. Renes
Ingrid B. Renes
2
*Department of Pediatrics, Division of Neonatology, Erasmus MC-Sophia, Rotterdam, 3015 GE, The Netherlands
2Correspondence may be addressed to either of these authors (email isabelle.vanseuningen@inserm.fr or i.renes@erasmusmc.nl).
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Publisher: Portland Press Ltd
Received:
November 17 2008
Revision Received:
February 09 2009
Accepted:
February 19 2009
Accepted Manuscript online:
February 19 2009
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 420 (2): 211–219.
Article history
Received:
November 17 2008
Revision Received:
February 09 2009
Accepted:
February 19 2009
Accepted Manuscript online:
February 19 2009
Citation
Nanda Burger-van Paassen, Audrey Vincent, Patrycja J. Puiman, Maria van der Sluis, Janneke Bouma, Günther Boehm, Johannes B. van Goudoever, Isabelle van Seuningen, Ingrid B. Renes; The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: implications for epithelial protection. Biochem J 1 June 2009; 420 (2): 211–219. doi: https://doi.org/10.1042/BJ20082222
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