Cf. Estivariz et al., GUT-TROPHIC EFFECTS OF KERATINOCYTE GROWTH-FACTOR IN RAT SMALL-INTESTINE AND COLON DURING ENTERAL REFEEDING, JPEN. Journal of parenteral and enteral nutrition, 22(5), 1998, pp. 259-267
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.