Purpose: Keratiuocyte growth factor (KGF) is important for intestinal epithelial (EC) growth. In the mocosa KGF is expressed by T-cell receptor (TCR) "yS+ IEL, and EC express KGF receptors (KGFR). The functional contribution of mucosal KGF has not been fully explored. We previously showed that IEL KGF mRNA was up-regulated in a short bowel syndrome (SBS) mouse model. We hypothesized that this increased expression would have impact in intestinal adaptation in SBS. This study examined the role of IEL KGF in the SBS model, and the expression of mucosal KGF and KGFR along the crypt-villus axis. Methods: Adult mice underwent a 55% mid-small bowel resection (SBS) or transsection without resection (control). After 7 days small bowel IEL and EC were harvested. ~,B + TCR IEL were isolated using flow cytometry. IEL KGF and EC KGFR expression were studied using real-time PCR. [EL KGF protein expression utilized immunoblotting. EC proliferation was determined by 8rdU incorporation. To assess the location of IEL KGF and EC KGFR mRNA expression (crypt, lower third (LV), and upper third of villus (UV)), laser capture microdissection was performed. Results are expressed as mean-+SD, ANOVA was used for statistics, P<O.05 considered significant. Results: SBS caused a significant increase in both IEL KGF and EC KGFR mRNA expression. Increases were confined to cells in the crypt and LV; no significant change was found in the UV (Table). 1EL KGF protein expression was also increased in SBS mice. EC proliferation increased by 33% m SBS mice vs. controls. To detemune the relative contribution of'y8 + TCR IEL KGF to EC growth, ',/B-TCR-knockout mice were used. Interestingly, BrdU positive cells were significantly (P<0.05) lower in 'yS-TCR / SBS mice (28.8- +1.6%) compared to wild-type SBS mice (36.3+7.6%). All proliferating cells were confined to the crypt level. Conclusions: IEL KGF and EC KGFR expression increased in this mouse SBS model, was predominantely in the crypt and lower villus, and appeared to have a significant impact on EC proliferation. These results provide important insight into the meehamsm of intestinal adaptation with SBS.