Intestinal Gene Expression in TNBS Treated Mice Using GeneChip and Subtractive cDNA Analysis: Implications for Crohn's Disease

抄録

So far it has proven difficult to identify a causative gene(s) or gene product initiating the events that lead to inflammation of the intestinal mucosa and, ultimately, progression to Crohn's disease (CD), an inflammatory bowel disease. However, gene transcripts identified in the intestine of trinitrobenzene sulfonic acid (TNBS)-treated mice might suggest a clue, and even represent candidate genes leading to inflammation and mucosal damage, and to subsequent fibrosis. In the present study, DNA microarray (13000 transcripts) methodology was applied to mucosal RNA extracted from TNBS-treated mice, some transcripts of which were validated via cDNA subtraction and RT-PCR analyses. Intestinal biopsy samples from CD patients were then analyzed using cDNA mini-array (1300 cDNAs), focusing on gene transcripts associated with cancer and immunity. Mini-array results revealed transcript changes similar and also dissimilar to those found from the DNA microarray analysis. These changes, previously known or newly identified, possibly occurring during the initial and progressive stages of inflammatory conditions may provide a clue to identify marker transcripts and/or targets for the development of future gene therapy.