Increases in nup 475 and c-jun Are Early Molecular Events That Precede the Adaptive Hyperplastic Response After Small Bowel Resection

Abstract

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. 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. 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. 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. 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.