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MicroRNA miR-16 is anti-proliferative in enterocytes and exhibits diurnal rhythmicity in intestinal crypts

ABSTRACT: This is the first report to document circadian rhythmicity of specific microRNAs in rat jejunum. Our data provide a link between the anti-proliferative microRNA miR-16 and the intestinal proliferation rhythm and point to miR-16 as an important regulator of proliferation in jejunal crypts. This function may be essential to match proliferation and absorptive capacity with nutrient availability.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE20603 | GEO | 2010/08/13

SECONDARY ACCESSION(S): PRJNA124775

REPOSITORIES: GEO

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Project description:Background and Aims: Although the zinc finger transcription factor GATA4 has been implicated in regulating jejunal gene expression, the contribution of GATA4 in controlling jejunal physiology has not been addressed. Methods: We generated mice in which the Gata4 gene was specifically deleted in the small intestinal epithelium. Measurements of plasma cholesterol and phospholipids, intestinal absorption of dietary fat and cholesterol, and gene expression were performed on these animals. Results: Mice lacking GATA4 in the intestine displayed a dramatic block in their ability to absorb cholesterol and dietary fat. Comparison of the global gene expression profiles of control jejunum, control ileum, and GATA4 null jejunum by gene array analysis demonstrated that GATA4 null jejunum lost expression of 53% of the jejunal-specific gene set and gained expression of 47% of the set of genes unique to the ileum. These alterations in gene expression included a decrease in mRNAs encoding lipid and cholesterol transporters as well as an increase in mRNAs encoding proteins involved in bile acid absorption. Conclusion: Our data demonstrate that GATA4 is essential for jejunal function including fat and cholesterol absorption and confirm that GATA4 plays a pivotal role in determining jejunal versus ileal identity. Experiment Overall Design: Total RNA was harvested from the following sources and used to Affymetrix array analysis following manufacturer defined protocols: Experiment Overall Design: control jejunum (Gata4loxP/+VilCre), 3 male mice, adult (6-8 wk) Experiment Overall Design: mutant jejunum (Gata4loxP/-VilCre), 3 male mice, adult (6-8 wk) Experiment Overall Design: control ileum (Gata4loxP/+VilCre), 3 male mice, adult (6-8 wk). Experiment Overall Design: A total of nine Mouse Genome 430_2.0 arrays were hybridized for this study. Experiment Overall Design: Jejunum was defined as 10 cm from the pyloric sphincter, and ileum was defined as 1 cm from the cecum. The animals used to harvest control jejunum and ileum were independent of each other.

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MicroRNA miR-16 is anti-proliferative in enterocytes and exhibits diurnal rhythmicity in intestinal crypts

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