Premium
Regulation of the intestinal mucin MUC2 expression by short chain fatty acids: implications for epithelial protection
Author(s) -
Burgervan Paassen Nanda,
Vincent Audrey,
Puiman Patrycja J,
Sluis Maria,
Bouma Janneke,
Boehm Gunther,
Van Goudoever Johannes B,
Van Seuningen Isabelle,
Renes Ingrid B
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.109.5
Subject(s) - butyrate , mucin 2 , mucin , chemistry , acetylation , chromatin immunoprecipitation , microbiology and biotechnology , methylation , dna methylation , histone , gene expression , biology , biochemistry , promoter , gene , fermentation
Short chain fatty acids (SCFAs) influence epithelial‐specific gene expression. We hypothesize that SCFAs affect mucin MUC2 expression and thereby epithelial protection. Aim: Study the effects of SCFAs on MUC2 expression. Methods LS174T cells were treated with SCFAs. MUC2 mRNA levels and stability and MUC2 protein expression were analyzed. SCFA‐responsive regions and cis‐elements within the MUC2 promoter were identified by transfection and gel shift assays. Effects on histone H3/H4 status at the MUC2 promoter were established by chromatin immunoprecipitation. Results Both 1 mM butyrate and propionate induced an increase in MUC2 mRNA levels. MUC2 mRNA levels returned to basal levels after incubation with 5‐15 mM of butyrate. This decrease was not due to loss of RNA stability. At 5‐15 mM of propionate MUC2 mRNA levels remained high. Promoter regulation studies revealed a butyrate‐responsive region in the MUC2 promoter containing an active AP1 cis‐element at ‐818/‐808 that mediates butyrate‐induced activation of the promoter. MUC2 regulation by butyrate at 10‐15 mM was associated with increased acetylation of histone H3/H4 and methylation of H3 at the promoter. Conclusion 1 mM of butyrate and 1‐15 mM of propionate increase MUC2 expression. The effects of butyrate on MUC2 mRNA are mediated via AP‐1 and acetylation/methylation of histones. Thus SCFAs affect MUC2 expression and thereby intestinal protection.