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Mixed Primary Cultures of Murine Small Intestine Intended for the Study of Gut Hormone Secretion and Live Cell Imaging of Enteroendocrine Cells
Published on: April 20, 2017
Short-chain fatty acids regulate IGF-binding protein secretion by intestinal epithelial cells
A Nishimura1, M Fujimoto, S Oguchi
1Developmental Gastroenterology Laboratory, Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Harvard Clinical Nutrition Research Center, Charlestown, Massachusetts 02129, USA.
Short-chain fatty acids, like butyrate, alter gastrointestinal epithelial cells' secretion of insulin-like growth factor-binding proteins (IGFBPs). This impacts cell signaling and is linked to histone acetylation.
Area of Science:
- Gastroenterology
- Molecular Biology
- Cell Biology
Background:
- Gastrointestinal epithelial cells secrete insulin-like growth factor (IGF)-binding proteins (IGFBPs).
- IGFBPs regulate IGF actions on cell proliferation and differentiation.
- Short-chain fatty acids (SCFAs) are bacterial metabolites from dietary carbohydrates.
Purpose of the Study:
- To investigate if SCFAs alter IGFBP secretion patterns in gastrointestinal epithelial cells.
- To understand the mechanism by which luminal molecules regulate epithelial cell signaling.
Main Methods:
- Utilized the Caco-2 intestinal epithelial cell line.
- Administered butyrate (an SCFA) and trichostatin A.
- Measured IGFBP secretion, mRNA accumulation, and histone acetylation.
Main Results:
- Butyrate increased IGFBP-2 secretion and decreased IGFBP-3 secretion in a dose-dependent and reversible manner.
- Changes in IGFBP secretion were due to altered synthesis, not cell sorting.
- SCFA and trichostatin A stimulation of IGFBP-2 correlated with histone acetylation.
Conclusions:
- Intestinal epithelial cells modify IGFBP secretion in response to SCFAs.
- This suggests a mechanism for luminal molecule regulation of gastrointestinal cell signaling.
- Histone acetylation may play a role in SCFA-mediated IGFBP regulation.
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