Gut-trophic effects of keratinocyte growth factor in rat small intestine and colon during enteral refeeding

Keratinocyte growth factor (KGF) induces proliferation of gut epithelium in rat models, but KGF-nutrient interactions have not been studied. An experimental model of fasting-induced gut atrophy followed by different levels of enteral refeeding was used to investigate the influence of nutrient availability on the gut-trophic effects of exogenous KGF.

After a 3-day fast, rats were enterally refed either ad libitum or at 25% of ad libitum intake for 3 subsequent days. Either intraperitoneal KGF (5 mg/kg/d) or saline was given in each dietary regimen. Wet weight, DNA, and protein content were measured as indices of full-thickness cellularity in duodenum, jejunum, ileum, and colon. Villus height in small bowel segments and crypt depth in all gut tissues were measured as specific indices of mucosal growth.

Refeeding at 25% of ad libitum intake significantly decreased full-thickness cellularity and mucosal growth indices in duodenum, jejunum, and ileum. In the colon, only protein content fell significantly and crypt depth was maintained. KGF administration during 25% refeeding did not alter full-thickness indices in any small bowel segment or affect jejunal mucosal growth. In contrast, KGF normalized duodenal villus height (p < .01) and duodenal and ileal crypt depth (p < .05) only in the 25%-refed model. KGF significantly increased ileal villus height in both ad libitum and 25%-refed rats (by 43% and 48%, respectively, p < .05) and markedly increased colonic cellularity and mucosal crypt depth with both levels of refeeding (p < .01).

Rat small bowel growth is more sensitive than colon to the level of enteral refeeding after a 3-day fast. KGF administration does not affect jejunal growth, but specifically prevents atrophy of duodenal and ileal mucosa during hypocaloric, hyponitrogenous refeeding. In ileum and colon, some KGF-mediated growth responses are independent of the level of enteral refeeding. Thus gut-trophic effects of KGF and KGF interactions with the level of nutrient intake are tissue-specific.