Proteasome gene upregulation: a possible mechanism for intestinal adaptation.
OBJECTIVE
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.
Otterburn
David M
DM
Department of Surgery, Thomas Jefferson University, Philadelphia, PA 19134-1095, USA.
Arthur
L Grier
LG
Timmapuri
Shaheen J
SJ
McCahan
Suzanne M
SM
Schwartz
Marshall Z
MZ
D000222:Adaptation, Physiological / Q000235:genetics*; D000714:Anastomosis, Surgical; D000818:Animals; D049109:Cell Proliferation; D015870:Gene Expression; D007408:Intestinal Absorption / Q000235:genetics* / Q000502:physiology; D007413:Intestinal Mucosa / Q000166:cytology* / Q000201:enzymology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012778:Short Bowel Syndrome / Q000503:physiopathology*; D015854:Up-Regulation
D012333:RNA, Messenger; D046988:Proteasome Endopeptidase Complex