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2006 Abstracts: Molecular analysis of colonic transformation in the ileum after total colectomy in rats
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Molecular analysis of colonic transformation in the ileum after total colectomy in rats
Kouhei Fukushima, Sho Haneda, Yuji Funayama, Chikashi Shibata, Ken-ichi Takahashi, Hitoshi Ogawa, Iwao Sasaki; Surgery, Tohoku University, Graduate School of Medicine, Sendai, Japan

Background. Colonic transformation is thought to be an altered phenotype in the ileum following total colectomy (TC) but has not been well addressed at molecular level. We previously demonstrated increased plasma aldosterone levels concomitant with the induction of molecules essential for sodium and water absorption in the rat model of TC. However, TC may result in a variety of alterations in intestinal function except for electrolyte transport. Methods. Ileal and/or colonic epithelial cells were isolated from control, TC (four weeks after surgery) and aldosterone-infused rats. Epithelial gene expression was compared between the ileum and distal colon in control rats by CodeLink Bioarrays (UniSet Rat 1 containing 10,060 elements, Motorola Inc., Schaumberg , IL ). Genes were categorized into “colonic”, “common”, and “ileal” genes according to signal intensity with more than 3-fold difference. Then, ileal gene expressions in (a) the control and TC rats and (b) the control and aldosterone-infused rats were compared to detect altered genes or assess the role of aldosterone in intestinal adaptation. We assessed the mRNA expression of MUC 3, an induced “colonic” gene, and lysozyme, an induced “ileal” gene following TC, by quantitative RT-PCR. Results. A total of 6,109 genes were categorized into “colonic” (627), “common” (5103) or “ileal” (379) gene pools. A comparison of the control and TC rats yielded 82 and 91 genes that were induced and suppressed in the ileum following TC, respectively. Thirty-five % of them were associated with “colon-like” transformation, i.e., the induction of “colonic” genes or the suppression of “ileal” genes. The expressions of MUC3 and lysozyme mRNAs were significantly enhanced in the ileum following. In comparison, aldosterone infusion modulated a total of only 21 genes in the ileum. Conclusion. The present data clearly demonstrate that intestinal adaptation four weeks following TC is characterized, at least in part, by a “colon-like” transformation, i.e., ileal epithelial cells assuming a partial colonic phenotype, as well as losing a portion of the ileal phenotype. However, epithelial cells in the remnant ileum adapt to the TC-altered environment by inducing effective molecules regardless of their initial “colonic”, “common”, or “ileal” nature. Circulating aldosterone appears to play a part of roles in altering and/or adapting gene expression in intestinal epithelium.


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