Butyrate transcriptionally enhances peptide transporter PepT1 expression and activity.

<h4>Background</h4>PepT1, an intestinal epithelial apical di/tripeptide transporter, is normally expressed in the small intestine and induced in colon during chronic inflammation. This study aimed at investigating PepT1 regulation by butyrate, a short-chain fatty acid produced by commens...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Guillaume Dalmasso, Hang Thi Thu Nguyen, Yutao Yan, Laetitia Charrier-Hisamuddin, Shanthi V Sitaraman, Didier Merlin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/505732b876954229bd02003aba6c64dd
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:505732b876954229bd02003aba6c64dd
record_format	dspace
spelling	oai:doaj.org-article:505732b876954229bd02003aba6c64dd2021-11-25T06:11:56ZButyrate transcriptionally enhances peptide transporter PepT1 expression and activity.1932-620310.1371/journal.pone.0002476https://doaj.org/article/505732b876954229bd02003aba6c64dd2008-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18575574/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>PepT1, an intestinal epithelial apical di/tripeptide transporter, is normally expressed in the small intestine and induced in colon during chronic inflammation. This study aimed at investigating PepT1 regulation by butyrate, a short-chain fatty acid produced by commensal bacteria and accumulated inside inflamed colonocyte.<h4>Results</h4>We found that butyrate treatment of human intestinal epithelial Caco2-BBE cells increased human PepT1 (hPepT1) promoter activity in a dose- and time-dependent manner, with maximal activity observed in cells treated with 5 mM butyrate for 24 h. Under this condition, hPepT1 promoter activity, mRNA and protein expression levels were increased as assessed by luciferase assay, real-time RT-PCR and Western blot, respectively. hPepT1 transport activity was accordingly increased by approximately 2.5-fold. Butyrate did not alter hPepT1 mRNA half-life indicating that butyrate acts at the transcriptional level. Molecular analyses revealed that Cdx2 is the most important transcription factor for butyrate-induced increase of hPepT1 expression and activity in Caco2-BBE cells. Butyrate-activated Cdx2 binding to hPepT1 promoter was confirmed by gel shift and chromatin immunoprecipitation. Moreover, Caco2-BBE cells overexpressing Cdx2 exhibited greater hPepT1 expression level than wild-type cells. Finally, treatment of mice with 5 mM butyrate added to drinking water for 24 h increased colonic PepT1 mRNA and protein expression levels, as well as enhanced PepT1 transport activity in colonic apical membranes vesicles.<h4>Conclusions</h4>Collectively, our results demonstrate that butyrate increases PepT1 expression and activity in colonic epithelial cells, which provides a new understanding of PepT1 regulation during chronic inflammation.Guillaume DalmassoHang Thi Thu NguyenYutao YanLaetitia Charrier-HisamuddinShanthi V SitaramanDidier MerlinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 6, p e2476 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Guillaume Dalmasso Hang Thi Thu Nguyen Yutao Yan Laetitia Charrier-Hisamuddin Shanthi V Sitaraman Didier Merlin Butyrate transcriptionally enhances peptide transporter PepT1 expression and activity.
description	<h4>Background</h4>PepT1, an intestinal epithelial apical di/tripeptide transporter, is normally expressed in the small intestine and induced in colon during chronic inflammation. This study aimed at investigating PepT1 regulation by butyrate, a short-chain fatty acid produced by commensal bacteria and accumulated inside inflamed colonocyte.<h4>Results</h4>We found that butyrate treatment of human intestinal epithelial Caco2-BBE cells increased human PepT1 (hPepT1) promoter activity in a dose- and time-dependent manner, with maximal activity observed in cells treated with 5 mM butyrate for 24 h. Under this condition, hPepT1 promoter activity, mRNA and protein expression levels were increased as assessed by luciferase assay, real-time RT-PCR and Western blot, respectively. hPepT1 transport activity was accordingly increased by approximately 2.5-fold. Butyrate did not alter hPepT1 mRNA half-life indicating that butyrate acts at the transcriptional level. Molecular analyses revealed that Cdx2 is the most important transcription factor for butyrate-induced increase of hPepT1 expression and activity in Caco2-BBE cells. Butyrate-activated Cdx2 binding to hPepT1 promoter was confirmed by gel shift and chromatin immunoprecipitation. Moreover, Caco2-BBE cells overexpressing Cdx2 exhibited greater hPepT1 expression level than wild-type cells. Finally, treatment of mice with 5 mM butyrate added to drinking water for 24 h increased colonic PepT1 mRNA and protein expression levels, as well as enhanced PepT1 transport activity in colonic apical membranes vesicles.<h4>Conclusions</h4>Collectively, our results demonstrate that butyrate increases PepT1 expression and activity in colonic epithelial cells, which provides a new understanding of PepT1 regulation during chronic inflammation.
format	article
author	Guillaume Dalmasso Hang Thi Thu Nguyen Yutao Yan Laetitia Charrier-Hisamuddin Shanthi V Sitaraman Didier Merlin
author_facet	Guillaume Dalmasso Hang Thi Thu Nguyen Yutao Yan Laetitia Charrier-Hisamuddin Shanthi V Sitaraman Didier Merlin
author_sort	Guillaume Dalmasso
title	Butyrate transcriptionally enhances peptide transporter PepT1 expression and activity.
title_short	Butyrate transcriptionally enhances peptide transporter PepT1 expression and activity.
title_full	Butyrate transcriptionally enhances peptide transporter PepT1 expression and activity.
title_fullStr	Butyrate transcriptionally enhances peptide transporter PepT1 expression and activity.
title_full_unstemmed	Butyrate transcriptionally enhances peptide transporter PepT1 expression and activity.
title_sort	butyrate transcriptionally enhances peptide transporter pept1 expression and activity.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/505732b876954229bd02003aba6c64dd
work_keys_str_mv	AT guillaumedalmasso butyratetranscriptionallyenhancespeptidetransporterpept1expressionandactivity AT hangthithunguyen butyratetranscriptionallyenhancespeptidetransporterpept1expressionandactivity AT yutaoyan butyratetranscriptionallyenhancespeptidetransporterpept1expressionandactivity AT laetitiacharrierhisamuddin butyratetranscriptionallyenhancespeptidetransporterpept1expressionandactivity AT shanthivsitaraman butyratetranscriptionallyenhancespeptidetransporterpept1expressionandactivity AT didiermerlin butyratetranscriptionallyenhancespeptidetransporterpept1expressionandactivity
_version_	1718414038587670528

Butyrate transcriptionally enhances peptide transporter PepT1 expression and activity.

Ejemplares similares