Journal of Molecular Medicine

, Volume 85, Issue 7, pp 733–743 | Cite as

Molecular defense mechanisms of Barrett’s metaplasia estimated by an integrative genomics

  • Jerzy Ostrowski
  • Michal Mikula
  • Jakub Karczmarski
  • Tymon Rubel
  • Lucjan S. Wyrwicz
  • Piotr Bragoszewski
  • Pawel Gaj
  • Michal Dadlez
  • Eugeniusz Butruk
  • Jaroslaw Regula
Original Article

Abstract

Barrett’s esophagus is characterized by the replacement of squamous epithelium with specialized intestinal metaplastic mucosa. The exact mechanisms of initiation and development of Barrett’s metaplasia remain unknown, but a hypothesis of “successful adaptation” against noxious reflux components has been proposed. To search for the repertoire of adaptation mechanisms of Barrett’s metaplasia, we employed high-throughput functional genomic and proteomic methods that defined the molecular background of metaplastic mucosa resistance to reflux. Transcriptional profiling was established for 23 pairs of esophageal squamous epithelium and Barrett’s metaplasia tissue samples using Affymetrix U133A 2.0 GeneChips and validated by quantitative real-time polymerase chain reaction. Differences in protein composition were assessed by electrophoretic and mass-spectrometry-based methods. Among 2,822 genes differentially expressed between Barrett’s metaplasia and squamous epithelium, we observed significantly overexpressed metaplastic mucosa genes that encode cytokines and growth factors, constituents of extracellular matrix, basement membrane and tight junctions, and proteins involved in prostaglandin and phosphoinositol metabolism, nitric oxide production, and bioenergetics. Their expression likely reflects defense and repair responses of metaplastic mucosa, whereas overexpression of genes encoding heat shock proteins and several protein kinases in squamous epithelium may reflect lower resistance of normal esophageal epithelium than Barrett’s metaplasia to reflux components. Despite the methodological and interpretative difficulties in data analyses discussed in this paper, our studies confirm that Barrett’s metaplasia may be regarded as a specific microevolution allowing for accumulation of mucosal morphological and physiological changes that better protect against reflux injury.

Keywords

Barrett’s esophagus Defense mechanisms Gene expression Microarrays Proteomics Integrative genomics 

Supplementary material

109_2007_176_MOESM1_ESM.pdf (664 kb)
Supplementary Figures (PDF 679 kb)
109_2007_176_MOESM2_ESM.pdf (132 kb)
Supplementary materials (PDF 135 kb)
109_2007_176_MOESM3_ESM.pdf (551 kb)
Supplementary Tables (PDF 1.2 mb)

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Jerzy Ostrowski
    • 1
  • Michal Mikula
    • 1
  • Jakub Karczmarski
    • 1
  • Tymon Rubel
    • 2
  • Lucjan S. Wyrwicz
    • 1
  • Piotr Bragoszewski
    • 1
  • Pawel Gaj
    • 1
  • Michal Dadlez
    • 3
  • Eugeniusz Butruk
    • 1
  • Jaroslaw Regula
    • 1
  1. 1.Department of Gastroenterology, Medical Center for Postgraduate EducationMaria Sklodowska-Curie Memorial Cancer Center and Institute of OncologyWarsawPoland
  2. 2.Institute of RadioelectronicsWarsaw University of TechnologyWarsawPoland
  3. 3.Department of Biophysics, Institute of Biochemistry and BiophysicsPASWarsawPoland

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