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NSAID-induced antral ulcers are associated with distinct changes in mucosal gene expression.

Abstract：

BACKGROUND:The basis for individual variation in gastroduodenal vulnerability to NSAIDs is not well understood. AIM:To assess whether a gene expression signature is associated with susceptibility to gastroduodenal ulcerations. METHODS:Twenty-five Helicobacter pylori negative adults were treated for 7 days with naproxen 500 mg b.d. Subjects underwent baseline and post-treatment endoscopy, during which biopsies were taken from antrum and duodenum. RNA extraction and cDNA synthesis were performed, followed by PCR of 23 genes relevant to mucosal injury and repair. Fold changes in gene expression were compared between subjects who developed ulcers and those who did not. RESULTS:Compared with subjects who did not develop ulcers (n = 18), subjects who developed antral ulcers (n = 7) had significantly greater mucosal up-regulation of interleukin-8 [Fold change = 33.5 (S.E.M. = 18.5) vs. -7.7 (3.2)] and of cyclo-oxygenase-2 [2.3 (1.7) vs. -10.8 (2.2)]. Conversely, non-ulcer subjects had significantly greater up-regulation of toll-like receptor-4, cyclo-oxygenase-1 and hepatocyte growth factor [14.0 (2.2) vs. -0.8 (1.0), 9.8 (2.4) vs. 0.0 (0.7) and 8.2 (2.6) vs. -2.2 (0.3) respectively]. CONCLUSIONS:NSAID-induced antral ulcers are associated with a specific pattern of gastroduodenal mucosal gene expression. These patterns may provide an insight into the molecular basis of individual susceptibility to mucosal injury.

journal_name

Aliment Pharmacol Ther

journal_title

Alimentary pharmacology & therapeutics

authors

Desai JC,Goo T,Fukata M,Sanyal S,Dikman A,Miller K,Cohen L,Brooks A,Wang Q,Abreu MT,Aisenberg J

doi

10.1111/j.1365-2036.2009.04000.x

subject

Has Abstract

pub_date

2009-07-01 00:00:00

pages

71-81

issue

1

eissn

0269-2813

issn

1365-2036

pii

APT4000

journal_volume

30

pub_type

杂志文章

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