Proteasome gene upregulation: A possible mechanism for intestinal adaptation

Background/Purpose: The mechanisms that control intestinal adaptation remain unknown. To better understand the adaptive process, microarray technology was used to analyze gene expression in a rat model of intestinal adaptation. Methods: Adult male Sprague-Dawley rats underwent either a massive small bowel resection (70%) with anastomosis or a sham operation with small bowel transection and reanastomosis. After 21 days, ileal mucosa RNA was extracted. Individual RNA samples (n = 5 per group) were labeled and hybridized to 10 separate RAE 230A rat GeneChips. The signal values were calculated and the 2 groups were compared using a t test with the multiple testing correction of Benjamini and Hochberg (false discovery rate of 10%). Probe sets were analyzed for overrepresented physiologic pathways using Expression Analysis Systematic Explorer (EASE). Results: Of the 15,866 probe sets on the RAE 230A GeneChip, 5437 probe sets were unexpressed and excluded. Of the remaining 10,429 probe sets, several overrepresented pathways (EASE score <0.01 after Bonferroni correction) were identified. Further analysis revealed that 13 probe sets related to proteasome degradation (an enzyme complex implicated in the regulation of cell proliferation) were significantly upregulated in the intestinal adaptation group compared to the sham group. Conclusions: Proteasomes may play a critical role in regulating the proliferation of intestinal mucosa during intestinal adaptation.