Increases in nup475 and c-jun are early molecular events that precede the adaptive hyperplastic response after small bowel resection.

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OBJECTIVE: The authors determined whether increases of nup475 and c-jun gene expression occur after small bowel resection and whether these changes are specific to the gut. SUMMARY BACKGROUND DATA: Massive small bowel resection (SBR) is characterized by adaptive proliferation of the remaining gut mucosa; the molecular signals responsible for this adaptive hyperplasia are unknown. Increases in the "immediate-early genes" nup475 and c-jun are noted in some proliferating tissues; however, alterations in the expression of these genes have not been described in the gut after SBR. METHODS: Rats underwent either a 70% proximal SBR or intestinal transection with reanastomosis (SHAM) and were then killed over a time course (0.5, 2, and 24 hours). The ileum, duodenum, colon, and kidneys were removed and RNA was extracted for Northern hybridization. RESULTS: The authors found that steady-state mRNA levels of both nup475 and c-jun were increased 81% and 62%, respectively, in the ileal remnant at 2 hours in rats after SBR compared with the SHAM group. In addition, nup475 was increased 101% in the duodenum at 24 hours and 31% in the colon at 0.5 hours in rats after SBR. In contrast, neither gene was increased in the kidney. CONCLUSIONS: Increases in steady-state levels of nup475 and c-jun are limited to the gut after SBR, and the timing and magnitude of these changes differ, depending on the gut segment. Finally, the rapid and nutrient-independent increases of nup475 and c-jun suggest an important role for these genes as early molecular signals that participate in the adaptive hyperplasia occurring in the gut remnant after SBR.

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