Dickkopf homologs in squamous mucosa of esophagitis patients are overexpressed compared with Barrett's patients and healthy controls.
OBJECTIVE
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.
Ali
Irshad
I
Dysphagia Institute, Division of Gastroenterology and Hepatology, Medical College of Milwaukee, Wisconsin 53226, USA.
Rafiee
Parvaneh
P
Hogan
Walter J
WJ
Jacob
Howard J
HJ
Komorowski
Richard A
RA
Haasler
George B
GB
Shaker
Reza
R
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001471:Barrett Esophagus / Q000235:genetics*; D015153:Blotting, Western; D016022:Case-Control Studies; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D004941:Esophagitis / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D006863:Hydrogen-Ion Concentration; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
C501126:DKK1 protein, human; C442333:DKK4 protein, human; D036341:Intercellular Signaling Peptides and Proteins