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

  1. J. C. DESAI1,
  2. T. GOO1,
  3. M. FUKATA2,
  4. S. SANYAL1,
  5. A. DIKMAN1,
  6. K. MILLER1,
  7. L. COHEN1,
  8. A. BROOKS3,
  9. Q. WANG3,
  10. M. T. ABREU2,
  11. J. AISENBERG1

Article first published online: 19 MAR 2009

DOI: 10.1111/j.1365-2036.2009.04000.x

Issue

Alimentary Pharmacology & Therapeutics

Alimentary Pharmacology & Therapeutics

Volume 30, Issue 1, pages 71–81, July 2009

Additional Information

How to Cite

DESAI, J. C., GOO, T., FUKATA, M., SANYAL, S., DIKMAN, A., MILLER, K., COHEN, L., BROOKS, A., WANG, Q., ABREU, M. T. and AISENBERG, J. (2009), NSAID-induced antral ulcers are associated with distinct changes in mucosal gene expression. Alimentary Pharmacology & Therapeutics, 30: 71–81. doi: 10.1111/j.1365-2036.2009.04000.x

Author Information

  1. 1

    Department of Medicine (Division of Gastroenterology), The Mount Sinai Medical Center, New York, NY, USA

  2. 2

    Division of Gastroenterology, University of Miami Miller School of Medicine, Miami, FL, USA

  3. 3

    Environmental and Occupational Health Science Institute, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ, USA

*Dr J. Aisenberg, 311 East 79th Street, New York, NY 10021, USA. E-mail: j.aisenberg@nyga.md

Publication History

  1. Issue published online: 15 JUN 2009
  2. Article first published online: 19 MAR 2009
  3. Publication data Submitted 11 November 2008 First decision 23 November 2008 Resubmitted 5 February 2009, 14 March 2009 Accepted 16 March 2009 Epub Accepted Article 19 March 2009

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Summary

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.

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