HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/6/G1106    most recent 00158.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Jovov, B. Articles by Orlando, R. C. Search for Related Content PubMed PubMed Citation Articles by Jovov, B. Articles by Orlando, R. C.

TRANSLATIONAL PHYSIOLOGY

Claudin-18: a dominant tight junction protein in Barrett's esophagus and likely contributor to its acid resistance

¹Department of Medicine, ²The Center for Environmental Medicine, Asthma and Lung Biology, ³Department of Pediatrics, and ⁴Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Submitted 11 April 2007 ; accepted in final form 8 October 2007

ABSTRACT

Barrett's esophagus (BE) is a specialized columnar epithelium (SCE) that develops as replacement for damaged squamous epithelium (SqE) in subjects with reflux disease, and as such it is apparently more acid resistant than SqE. How SCE resists acid injury is poorly understood; one means may involve altered tight junctions (TJs) since the TJ in SqE is an early target of attack and damage by acid in reflux disease. To assess this possibility, quantitative RT-PCR for 21 claudins was performed on endoscopic biopsies on SCE of BE and from healthy SqE from subjects without esophageal disease. In SCE, Cldn-18 was the most highly expressed at the mRNA level and this finding is paralleled by marked elevation in protein expression on immunoblots. In contrast in SqE, Cldn-18 was minimally expressed at the mRNA level and undetectable at the protein level. Immunofluorescence studies showed membrane localization of Cldn-18 and colocalization with the tight junction protein, zonula occludens-1. When Cldn-18 was overexpressed in MDCK II cells and mounted as monolayers in Ussing chambers, it raised electrical resistance and, as shown by lower dilution potentials to a NaCl gradient and lower diffusion potentials to acidic gradients, selectively reduced paracellular permeability to both Na⁺ and H⁺ compared with parental MDCK cells. We conclude that Cldn-18 is the dominant claudin in the TJ of SCE and propose that the change from a Cldn-18-deficient TJ in SqE to a Cldn-18-rich TJ in SCE contributes to the greater acid resistance of BE.

claudin profiling; quantitative RT-PCR; paracellular permeability; stratified squamous epithelium

This article has been cited by other articles:

				K. Hormi-Carver, X. Zhang, H. Y. Zhang, R. H. Whitehead, L. S. Terada, S. J. Spechler, and R. F. Souza Unlike Esophageal Squamous Cells, Barrett's Epithelial Cells Resist Apoptosis by Activating the Nuclear Factor-{kappa}B Pathway Cancer Res., January 15, 2009; 69(2): 672 - 677. [Abstract] [Full Text] [PDF]

				U. Sahin, M. Koslowski, K. Dhaene, D. Usener, G. Brandenburg, G. Seitz, C. Huber, and O. Tureci Claudin-18 Splice Variant 2 Is a Pan-Cancer Target Suitable for Therapeutic Antibody Development Clin. Cancer Res., December 1, 2008; 14(23): 7624 - 7634. [Abstract] [Full Text] [PDF]

				X. Li, P. C. Galipeau, C. A. Sanchez, P. L. Blount, C. C. Maley, J. Arnaudo, D. A. Peiffer, D. Pokholok, K. L. Gunderson, and B. J. Reid Single Nucleotide Polymorphism-Based Genome-Wide Chromosome Copy Change, Loss of Heterozygosity, and Aneuploidy in Barrett's Esophagus Neoplastic Progression Cancer Prevention Research, November 1, 2008; 1(6): 413 - 423. [Abstract] [Full Text] [PDF]

				B. J. Reid Cancer Risk Assessment and Cancer Prevention: Promises and Challenges Cancer Prevention Research, September 1, 2008; 1(4): 229 - 232. [Full Text] [PDF]