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1 Human Nutrition and Gut Function Department, INRA, Nantes, France
2 U539, INSERM, Nantes, France
3 Food Safety and Nutrition Department, INRA, Jouy en josas, France
4 U560, INSERM, Lille, France
* To whom correspondence should be addressed. E-mail: hoebler{at}nantes.inra.fr.
The mucus layer covering the gastrointestinal mucosa is considered as the first line of defense against aggressions arising from the luminal content. It is mainly composed of high molecular weight glycoproteins called mucins. Butyrate, a short chain fatty acid produced during carbohydrate fermentation, has been shown to increase mucin secretion. The aim of this study was to test (i) whether butyrate regulates the expression of various MUC genes, which are coding for protein backbones of mucins, and (ii) if this effect depends on butyrate status as the major energy source of colonocytes. Butyrate was provided at the apical side of a human polarized colonic goblet cell line, HT29-Cl.16E, in glucose-rich or glucose-deprived medium. In glucoserich medium, butyrate significantly increased MUC3 and MUC5B expression (1.6 fold basal level for both genes), tended to decrease MUC5AC expression, and had no effect on MUC2 expression. In glucose-deprived medium, i.e. when butyrate was the only energy source available, MUC3 and MUC5B increase persisted while MUC5AC expression was significantly enhanced (3.7 fold basal level) and MUC2 expression was strikingly increased (23 fold basal level). Together, our findings show that butyrate is able to up-regulate colonic mucins at the transcriptional level, even better when it is the major energy source of the cells. Thus, the metabolism of butyrate in colonocytes is closely linked to some of its gene regulating effects. The distinct effects of butyrate according to the different MUC genes could influence the composition and properties of the mucus gel, and thus its protective function.
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