Literature DB >> 11976168

Distribution of the H+/peptide transporter PepT1 in human intestine: up-regulated expression in the colonic mucosa of patients with short-bowel syndrome.

Thomas R Ziegler1, Concepción Fernández-Estívariz, Li H Gu, Niloofar Bazargan, Kay Umeakunne, Timothy M Wallace, Emma E Diaz, Kathia E Rosado, Robert R Pascal, John R Galloway, Josiah N Wilcox, Lorraine M Leader.   

Abstract

BACKGROUND: Intestinal adaptation after massive bowel resection in animal models is characterized by increased gut-mucosal growth and expression of nutrient transporters. Few data about these indexes exist in humans with short-bowel syndrome (SBS).
OBJECTIVE: The objective was to compare small-bowel and colonic mucosal growth and expression of the peptide transporter PepT1 in adults with or without SBS.
DESIGN: Mucosal biopsy specimens were obtained from the small bowel and colon of 33 control subjects with intact intestine and from 13 SBS patients dependent on parenteral nutrition because of chronic malabsorption. Gut-mucosal crypt depth, villus height, and villus width were measured, and expression of PepT1 was determined by Northern blotting, in situ hybridization, and immunohistochemistry.
RESULTS: The indexes of small-bowel and colonic mucosal growth were not significantly different between the 2 groups. PepT1 expression was high in the apical region of duodenal, jejunal, and ileal villus epithelial cells; low in absorptive colonocytes; and not significantly different in the distal small intestine of the 2 groups. However, the abundance of PepT1 mRNA in the colon of SBS patients was more than 5-fold that in control subjects (P < 0.01).
CONCLUSIONS: Gut adaptation in SBS patients does not appear to involve an increase in gut-mucosal crypt depth or villus size. PepT1 is abundant along the small-bowel brush border in humans; expression in the colon indicates that the large intestine has a mechanism for luminal di- and tripeptide transport. Up-regulation of colonic PepT1 in SBS may adaptively improve accrual of malabsorbed di- and tripeptides, independent of changes in the mucosal surface area.

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Year:  2002        PMID: 11976168     DOI: 10.1093/ajcn/75.5.922

Source DB:  PubMed          Journal:  Am J Clin Nutr        ISSN: 0002-9165            Impact factor:   7.045


  46 in total

1.  Messenger RNA expression of transporter and ion channel genes in undifferentiated and differentiated Caco-2 cells compared to human intestines.

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Journal:  Pharm Res       Date:  2003-01       Impact factor: 4.200

Review 2.  The use of hormonal growth factors in the treatment of patients with short-bowel syndrome.

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3.  Intestinal adaptation for oligopeptide absorption via PepT1 after massive (70%) mid-small bowel resection.

Authors:  Srivats Madhavan; Jeffrey S Scow; Rizwan M Chaudhry; Munenori Nagao; Ye Zheng; Judith A Duenes; Michael G Sarr
Journal:  J Gastrointest Surg       Date:  2010-12-18       Impact factor: 3.452

4.  Changes induced in colonocytes by extensive intestinal resection in rats.

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Journal:  Dig Dis Sci       Date:  2006-02       Impact factor: 3.199

Review 5.  Apical/basolateral surface expression of drug transporters and its role in vectorial drug transport.

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Journal:  Pharm Res       Date:  2005-09-22       Impact factor: 4.200

Review 6.  Intestinal mucosal adaptation.

Authors:  Laurie Drozdowski; Alan B R Thomson
Journal:  World J Gastroenterol       Date:  2006-08-07       Impact factor: 5.742

Review 7.  Morphological, kinetic, membrane biochemical and genetic aspects of intestinal enteroplasticity.

Authors:  Laurie A Drozdowski; M Tom Clandinin; Alan B R Thomson
Journal:  World J Gastroenterol       Date:  2009-02-21       Impact factor: 5.742

Review 8.  Intestinal adaptation after massive intestinal resection.

Authors:  A R Weale; A G Edwards; M Bailey; P A Lear
Journal:  Postgrad Med J       Date:  2005-03       Impact factor: 2.401

9.  Impact of intestinal PepT1 on the kinetics and dynamics of N-formyl-methionyl-leucyl-phenylalanine, a bacterially-produced chemotactic peptide.

Authors:  Shu-Pei Wu; David E Smith
Journal:  Mol Pharm       Date:  2013-01-07       Impact factor: 4.939

10.  Species differences in the pharmacokinetics of cefadroxil as determined in wildtype and humanized PepT1 mice.

Authors:  Yongjun Hu; David E Smith
Journal:  Biochem Pharmacol       Date:  2016-03-12       Impact factor: 5.858

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