Keratinocyte growth factor (KGF) enhances early regrowth in a rat model of short bowel syndrome

Abstract

The effect of KGF on intestinal adaptation was evaluated in an experimental model of short bowel syndrome. Massive intestinal resection was performed in rats in which 85% of the small intestine was removed and the remaining ileal remnant anastomosed to the duodenal stump. Sham operated animals received only an anastomosis after transection. Resected and sham operated animals received 3 mg/kg KGF or vehicle daily for 3 days beginning the day following surgery, weighed daily and pair-fed to standardize the effect of lumenal nutrition. The response was evaluated by measurement of several indices of growth, cellularity and biochemical function in duodenal, jejunal and ileal segments. KGF augmented intestinal growth in the resected as well as the sham operated animal. However, in the case of resection, the weight of residual bowel was increased by 20% in KGF-treated animals. This was in addition to the adaptive hypertrophy that occurs in this resection model. Other indices of growth followed this trend and there were increases in mucosal thickness due to growth of both crypts and villi. The increase in cellularity was also evident by increases in cellular DNA and was accompanied by increased protein, and changes in the alkaline phosphatase and sucrase activities. These data show that KGF can enhance the early regrowth of the small intestine after resection and suggest that KGF may offer benefit to patients undergoing massive small bowel resection by facilitating post-operative intestinal adaptation. This research was funded by Amgen, Inc., Thousand Oaks, CA