Low-dose aspirin reduces the gene expression of gastrokine-1 in the antral mucosa of healthy subjects.
BACKGROUND
Gastrokine 1 (GKN1), one of the most abundant transcripts in normal stomach, is down-regulated by Helicobacter pylori infection. Aspirin (ASA), which is often used for secondary prevention of cardiovascular events, can damage gastric-duodenal mucosa within 1 or 2 h of ingestion.


OBJECTIVE
To study the gastric mucosal expression of GKN1 during acute low-dose ASA consumption.


METHODS
Ten H. pylori-negative human volunteers took 100 mg ASA per day for 1 week, and underwent multiple upper GI endoscopies. GKN1 expression was analysed in antral and corpus mucosa by quantitative reverse-transcriptase polymerase chain reaction, western blot and immunohistochemistry (IHC). Gastric mucosal damage was detected endoscopically and histologically.


RESULTS
Gastrokine 1 was similarly expressed in both antral and corpus mucosa. The use of low-dose ASA led to a significant decrease (3.07 a.u. vs. 0.23 a.u., P < 0.001) in antrum at day 7, while GKN1 transcript levels in corpus mucosa were slightly elevated (twofold, P < 0.005). Western blot and IHC confirmed these changes at the protein level. Furthermore, IHC revealed a vesicular staining pattern in the cytoplasm for GKN1 that was confirmed by transfected human gastric adenocarcinoma cell line expressing GKN1.


CONCLUSIONS
Our data demonstrated that low-dose ASA downregulates GKN1 expression specifically in antral mucosa.
Martin
G
G
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany.
Wex
T
T
Treiber
G
G
Malfertheiner
P
P
Nardone
G
G
D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D015536:Down-Regulation; D005753:Gastric Mucosa / Q000737:chemistry* / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D036361:Peptide Hormones / Q000032:analysis* / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011706:Pyloric Antrum; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013194:Staining and Labeling; D013997:Time Factors
C477000:GKN1 protein, human; D036361:Peptide Hormones; D010975:Platelet Aggregation Inhibitors; D001241:Aspirin