MicroRNA-92b regulates expression of the oligopeptide transporter PepT1 in intestinal epithelial cells. 2011

Guillaume Dalmasso, and Hang Thi Thu Nguyen, and Yutao Yan, and Hamed Laroui, and Moiz A Charania, and Tracy S Obertone, and Shanthi V Sitaraman, and Didier Merlin
Department of Medicine, Division of Digestive Diseases, Emory University School of Medicine, Atlanta GA 30322, USA. gdalmas@emory.edu

MicroRNAs (miRNAs), which are noncoding RNAs that posttranscriptionally inhibit expression of target genes, have recently emerged as important regulators of many cellular functions such as cell differentiation. The epithelial di/tripeptide membrane transporter PepT1 is expressed in highly differentiated cells (the villous tip) but not in undifferentiated cells (the crypt) of the small intestine. Here, we investigated the regulation of PepT1 expression by miRNAs and its functional consequences. We observed a reverse correlation between the expression levels of PepT1 and mature miRNA-92b (miR-92b) during the differentiation of intestinal epithelial Caco2-BBE cells, suggesting a miR-92b-mediated regulation of PepT1 expression. We demonstrate that miR-92b suppressed PepT1 expression at both mRNA and protein levels, with subsequent reduced PepT1 transport activity, in Caco2-BBE cells by directly targeting the PepT1 3'-untranslated region. In addition, miR-92b suppresses bacterial peptide-induced proinflammatory responses in intestinal epithelial cells by inhibiting PepT1 expression. Altogether, our study provides for the first time evidence for the regulation of PepT1 expression at a posttranscriptional level by miRNAs in intestinal epithelial cells during pathophysiological states.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D007413 Intestinal Mucosa Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI. Intestinal Epithelium,Intestinal Glands,Epithelium, Intestinal,Gland, Intestinal,Glands, Intestinal,Intestinal Gland,Mucosa, Intestinal
D009842 Oligopeptides Peptides composed of between two and twelve amino acids. Oligopeptide
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D003960 Diaminopimelic Acid A diamino derivative of heptanedioic acid with amino groups at C-2 and C-6 and the general formula (COOH)CH(NH2)CH2CH2CH2CH(NH2)(COOH). 2,6-Diaminopimelic Acid,2,6 Diaminopimelic Acid,Acid, 2,6-Diaminopimelic,Acid, Diaminopimelic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000074011 Peptide Transporter 1 A proton-coupled symporter that transports OLIGOPEPTIDES and DIPEPTIDES. It localizes to the brush-border membrane of the INTESTINAL EPITHELIUM and plays a critical role in the assimilation of dietary proteins. Hydrogen-Peptide Cotransporter PepT1,Intestinal H+-Peptide Cotransporter,PepT1 Protein,Pept-1 Transporter,SLC15A1 Protein,Solute Carrier Family 15 Member 1,hPEPT1 (Cotransporter),H+-Peptide Cotransporter, Intestinal,Hydrogen Peptide Cotransporter PepT1,Intestinal H+ Peptide Cotransporter,PepT1, Hydrogen-Peptide Cotransporter,Pept 1 Transporter,Transporter, Pept-1
D015536 Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Down-Regulation,Down-Regulation (Physiology),Downregulation,Down Regulation,Down-Regulation, Receptor
D018938 Caco-2 Cells Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells, such as ENTEROCYTES. These cells are valuable in vitro tools for studies related to intestinal cell function and differentiation. Caco 2 Cells,Caco-2 Cell,Cell, Caco-2,Cells, Caco-2
D027981 Symporters Membrane transporters that co-transport two or more dissimilar molecules in the same direction across a membrane. Usually the transport of one ion or molecule is against its electrochemical gradient and is "powered" by the movement of another ion or molecule with its electrochemical gradient. Co-Transporter,Co-Transporters,Symporter,Co Transporter,Co Transporters

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