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Updated: May 2, 2026
Author Spotlight: Studying the Epithelial Effects of Intestinal Inflammation In Vitro on Established Murine Colonoids
Published on: June 2, 2023
Colonic miRNA expression/secretion, regulated by intestinal epithelial PepT1, plays an important role in cell-to-cell
Saravanan Ayyadurai1, Moiz A Charania1, Bo Xiao1
1Department of Biology and Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, United States of America.
Abstract:
PepT1 is a member of the proton-oligopeptide cotransporter family SLC15, which mediates the transport of di/tripeptides from intestinal lumen into epithelial cells. MicroRNAs (miRNAs), a small noncoding RNAs (21-23 nucleotides), post-transcriptionally regulate gene expression by binding to the 3'-untranslated regions (UTRs) of their target mRNAs. Although the role of most miRNAs remains elusive, they have been implicated in vital cellular functions such as intestinal epithelial cells differentiation, proliferation, and apoptosis. In the present study, we investigated the effect of intestinal epithelial PepT1 expression on microRNA (miRNA) expression/secretion in the colons of control mice and in mice with experimentally induced colonic inflammation (colitis). The colonic miRNA expression was deregulated in both colitis and control mice but the deregulation of miRNA expression/secretion was specific to colonic tissue and did not affect other tissues such as spleen and liver. Intestinal epithelial PepT1-dependent deregulation of colonic miRNA expression not only affects epithelial cells but also other cell types, such as intestinal macrophages. Importantly, we found the miRNA 23b which was known to be involved in inflammatory bowel disease was secreted and transported between cells to impose a gene-silencing effect on recipient intestinal macrophages. Based on our data, we may conclude that the expression of a specific protein, PepT1, in the intestine affects local miRNA expression/secretion in the colon on a tissue specific manner and may play an important role during the induction and progression of colitis. Colonic miRNA expression/secretion, regulated by intestinal epithelial PepT1, could play a crucial role in cell-to-cell communication during colitis.
Insights
The peptide transporter PepT1 influences microRNA (miRNA) expression in the colon, impacting cell communication and potentially playing a role in colitis. This tissue-specific effect highlights miRNA
Area of Science:
- Gastroenterology
- Molecular Biology
- Cell Biology
Background:
- MicroRNAs (miRNAs) are small noncoding RNAs regulating gene expression post-transcriptionally.
- miRNAs are implicated in essential cellular functions including intestinal epithelial cell differentiation, proliferation, and apoptosis.
- The proton-oligopeptide cotransporter 1 (PepT1) mediates di/tripeptide transport in intestinal epithelial cells.
Purpose of the Study:
- To investigate the impact of intestinal epithelial PepT1 expression on miRNA expression and secretion in the colon.
- To determine if PepT1-mediated miRNA deregulation is specific to the colon during experimentally induced colitis.
- To explore the role of PepT1-dependent miRNAs in intercellular communication, particularly involving intestinal macrophages.
Main Methods:
- Comparative analysis of colonic miRNA expression in control and colitis-induced mice.
- Assessment of miRNA expression/secretion in spleen and liver tissues to determine tissue specificity.
- Investigation of PepT1's influence on miRNA expression in both epithelial cells and other cell types like macrophages.
- Identification and functional analysis of specific miRNAs, such as miRNA 23b, involved in intercellular communication.
Main Results:
- Colonic miRNA expression was deregulated in both control and colitis models, with specificity to the colonic tissue.
- PepT1-dependent miRNA deregulation affected not only epithelial cells but also other colonic cell types, including macrophages.
- Secreted miRNA 23b, known to be involved in inflammatory bowel disease, was found to mediate gene silencing in recipient intestinal macrophages.
- PepT1 expression in the intestine was shown to influence local miRNA expression/secretion in a tissue-specific manner.
Conclusions:
- Intestinal epithelial PepT1 expression significantly affects colonic miRNA expression and secretion in a tissue-specific manner.
- PepT1-regulated colonic miRNAs play a crucial role in cell-to-cell communication during colitis.
- These findings suggest PepT1 and its associated miRNA regulation are important factors in the induction and progression of colitis.
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