Faculty Collaboration Database

Dickkopf homologs in squamous mucosa of esophagitis patients are overexpressed compared with Barrett's patients and healthy controls. Am J Gastroenterol 2006 Jul;101(7):1437-48

Date

07/26/2006

Pubmed ID

16863544

DOI

10.1111/j.1572-0241.2006.00584.x

Scopus ID

2-s2.0-33745526343 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

OBJECTIVES: Esophageal mucosal response to acid exposure varies from minimal changes to erosions/ulcerations and Barrett's metaplasia. While differences in acid contact time have been suggested, the reason for these different responses is not completely understood. The aim of this study was to identify and compare gene expression differences between normal distal and proximal squamous esophageal mucosa (SM) in esophagitis patients with that of healthy controls and Barrett's patients.

METHODS: Gene microarray was performed on laser-capture microdissected epithelial cells isolated from biopsy specimens followed by real-time PCR. The effect of acidic pH (pH 4.5) on Dickkopf Homolog 1 (Dkk-1) expression in the human esophageal epithelial cell line (Het-1A) was determined.

RESULTS: Gene microarray analysis demonstrated that the upregulation of five genes in the distal compared with the proximal SM in esophagitis patients was greater than the healthy controls and Barrett's patients. Overexpression of Dkk-1 and Dkk-4 was further confirmed by real-time PCR. Dkk-1 and Dkk-4 mRNA levels in the distal SM of the esophagitis patients were 7.0- and 3.1-fold higher, respectively, than in the distal SM of the Barrett's patients and 4.1- and 4.1-fold higher than in healthy controls, respectively. Dkk-1 protein expression in the distal esophagitis SM was also higher than the Barrett's patients and healthy controls. Acidic pH exposure of Het-1A cells resulted in Dkk-1 upregulation at the level of both mRNA and protein.

CONCLUSIONS: Dkk-1 and Dkk-4 may potentially be involved in the development of different injuries in response to pathological gastroesophageal acid reflux.

Author List

Ali I, Rafiee P, Hogan WJ, Jacob HJ, Komorowski RA, Haasler GB, Shaker R

Author

Reza Shaker MD Assoc Provost, Sr Assoc Dean, Ctr Dir, Chief, Prof in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Analysis of Variance
Barrett Esophagus
Blotting, Western
Case-Control Studies
Cell Line
Enzyme-Linked Immunosorbent Assay
Esophagitis
Female
Gene Expression Profiling
Humans
Hydrogen-Ion Concentration
Intercellular Signaling Peptides and Proteins
Male
Middle Aged
Oligonucleotide Array Sequence Analysis
Prospective Studies
Reverse Transcriptase Polymerase Chain Reaction
Up-Regulation