Wnt/β-catenin signaling cascade down-regulation following massive small bowel resection in a rat

Growing evidence suggests that the Wnt/β-catenin signaling cascade is implicated in the control of stem cell activity, cell proliferation, lineage commitment, and cell survival during normal development and tissue regeneration of the gastrointestinal epithelium. The roles of this signaling cascade in stimulation of cell proliferation after massive small bowel resection are unknown. The purpose of this study was to evaluate the role of Wnt/β-catenin signaling during late stages of intestinal adaptation in a rat model of short bowel syndrome (SBS).

Male rats were divided into two groups: sham rats underwent bowel transection and SBS rats underwent a 75 % bowel resection. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined 2 weeks after operation. Illumina's digital gene expression analysis was used to determine Wnt/β-catenin signaling gene expression profiling. Twelve Wnt/β-catenin-related genes and β-catenin protein expression were determined using real-time PCR, western blotting and immunohistochemistry.

From the total number of 20,000 probes, 20 genes related to Wnt/β-catenin signaling were investigated. From these genes, seven genes were found to be up-regulated and eight genes to be down-regulated in SBS vs. sham animals with a relative change in gene expression level of 20 % or more. From 12 genes determined by real-time PCR, nine genes were down-regulated in SBS rats compared to control animals including target gene c-Myc. SBS rats also showed a significant decrease in β-catenin protein compared to control animals.

Two weeks following massive bowel resection in rats, Wnt/β-catenin signaling pathway is inhibited. In addition, it appears that cell differentiation rather than proliferation is most important in the late stages of intestinal adaptation.