GUT-TROPHIC EFFECTS OF KERATINOCYTE GROWTH-FACTOR IN RAT SMALL-INTESTINE AND COLON DURING ENTERAL REFEEDING

Background: Keratinocyte growth factor (KGF) induces proliferation of gut epithelium in rat models, but KGF-nutrient interactions have not b een studied. An experimental model of fasting-induced gut atrophy foll owed by different levels of enteral refeeding was used to investigate the influence of nutrient availability on the gut-trophic effects of e xogenous KGF. Methods: After a S-day fast, rats were enterally refed e ither 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 di etary regimen. Wet weight, DNA, and protein content were measured as i ndices of full-thickness cellularity in duodenum, jejunum, ileum, and colon. Villus height in small bowel segments and crypt depth in all gu t tissues were measured as specific indices of mucosal growth. Results : Refeeding at 25% of ad libitum intake significantly decreased full-t hickness cellularity and mucosal growth indices in duodenum, jejunum, and ileum. In the colon, only protein content fell significantly and c rypt 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 h eight (p < .01) and duodenal and ileal crypt depth (p < .05) only in t he 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 dep th with both levels of refeeding (p < .01). Conclusions: Rat small bow el growth is more sensitive than colon to the level of enteral refeedi ng after a S-day fast. KGF administration does not affect jejunal grow th, but specifically prevents atrophy of duodenal and ileal mucosa dur ing hypocaloric, hyponitrogenous refeeding. In ileum and colon, some K GF-mediated growth responses are independent of the level of enteral r efeeding. Thus gut-trophic effects of KGF and KGF interactions with th e level of nutrient intake are tissue-specific.