Detection of duodenal ulcer-associated genes in rats.

Unlabelled: We assessed the expression of about 8,000 known or unknown genes in the preulcerogenic stages of cysteamine-induced duodenal ulceration in rats, in comparison with the toxic but nonulcerogen ethanolamine. The most prominent gene changes were confirmed by custom gene blots, reverse transcriptase polymerase chain reaction (RT-PCR), real-time PCR, radio-immunoassay, Western blot, or enzyme-linked immunosorbent assay (ELISA), and the levels of their expression in other gastrointestinal organs such as ileum and colon were identified by real-time PCR. The time-course study after cysteamine showed 40 genes with marked changes, belonging to cell surface antigens, transcription factors, DNA binding proteins, ion channels, transport proteins, cellular receptors, and expressed sequence tags (i.e., unknown genes). In comparison with ethanolamine, these 40 genes changed by cysteamine only may represent ulcer-associated genes, such as endothelin receptor B, endothelin 1, caspase 3, transcription factors egr-1, Sp1, the angiogenic growth factors vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), and especially egr-1 and endothelin receptor B (ETRB) showed no changes in ileum and colon.

Conclusions: (1) These data suggest that duodenal ulcerogenesis may require the interaction of several genes leading to endothelial and epithelial cell injury, mucosal erosion, and ulcer; (2) these new findings may offer a new approach to the identification of potential ulcerogenic genes and provide new insights into the molecular mechanisms of duodenal ulceration.