Impact of gastro-esophageal reflux on mucin mRNA expression in the esophageal mucosa.
BACKGROUND
Changes in the expression of mucin genes in the esophageal mucosa associated with uncomplicated gastro-esophageal reflux disease have not been evaluated even though such changes could be associated with reflux-induced mucosal damage. We therefore sought to identify reflux-induced changes in mucin gene expression using a cell line and biopsies from the esophageal mucosa in patients with and without reflux.


METHODS
MUC-1, MUC-3, MUC-4, and MUC-5AC gene expressions were investigated in the HET-1A cell line following exposure to acid (pH 4) and/or bile (120 muM of a bile salt milieu), and in esophageal mucosal biopsies from controls, subjects with non-erosive gastro-esophageal reflux, and subjects with reflux associated with ulcerative esophagitis (erosive). The mucosal biopsies were also evaluated for IL-6 mRNA expression (inflammatory marker) and CK-14 mRNA expression (mucosal basal cell layer marker). Gene expression was determined using real-time reverse transcriptase-polymerase chain reaction analysis.


RESULTS
In the cell line studies, there were differences in mRNA levels for all of the evaluated mucins following treatment with either acid or the acid and bile combination. In the studies which evaluated tissue specimens, IL-6 and CK-14 mRNA levels increased according to degree of reflux pathology. The expression of MUC-1 and MUC-4 in mucosa from patients with erosive reflux was lower than in subjects without reflux and in patients with non-erosive reflux, whereas the expression of MUC-3 and MUC-5AC was increased (although these differences did not reach significance at p < 0.05). When mRNA expression data for tissue samples from all groups were combined, significant correlations were identified between IL-6 vs. CK-14 and IL-6 vs. MUC-3, MUC-3 vs. CK-14 and MUC-3 vs. MUC-5AC, and for MUC-1 vs. MUC-5AC. The correlation between IL-6 and CK-14 was also significant within the control and non-erosive reflux groups. The correlation between IL-6 and MUC-3 was significant within the control and erosive reflux groups, and the correlation between MUC-1 and MUC-5AC was significant within the erosive reflux group.


CONCLUSIONS
The results of this study suggest that the profile of mucin expression in the esophageal mucosa is influenced by the pH and composition of the gastro-esophageal reflux. Further work should explore the response of these genes to acid and bile reflux, and their role in the etiology of mucosal damage in gastro-esophageal reflux.
van Roon
Aafke H C
AH
Department of Surgery, Flinders Medical Centre, Flinders University, Room 3D211, Bedford Park, South Australia, 5042, Australia.
Mayne
George C
GC
Wijnhoven
Bas P L
BP
Watson
David I
DI
Leong
Mary P
MP
Neijman
Gabriëlle E
GE
Michael
Michael Z
MZ
McKay
Andrew R
AR
Astill
David
D
Hussey
Damian J
DJ
D001706:Biopsy; D002460:Cell Line; D004947:Esophagus / Q000378:metabolism* / Q000473:pathology; D005764:Gastroesophageal Reflux / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D009077:Mucins / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index
D009077:Mucins; D012333:RNA, Messenger