The effect of hepatocyte growth factor on intestinal adaption in an experimental model of short bowel syndrome.

PURPOSE: Nowadays, the standard therapy for patients with short bowel syndrome is parenteral nutrition (PN). Various growth factors have been tested to achieve weaning from prolonged PN administration. We evaluated the effect of hepatocyte growth factor (HGF) on structural intestinal adaptation and cell proliferation in a rat model of SBS.

METHODS

Thirty Sprague-Dawley rats were divided into three groups; group A rats (sham) underwent bowel transection, group B rats underwent a 75% bowel resection, and group C rats underwent the same procedure but were treated postoperatively with HGF. Histopathologic parameters of intestinal adaptation were determined, while microarray and rt-PCR analyses of ileal RNA were also performed.

RESULTS

Treatment with HGF resulted in significant increase in body weight, while the jejunal and ileal villus height and crypt depth were increased in HGF rats (36%, p < 0.05 and 27%, p < 0.05 respectively). Enterocyte proliferation was also significantly increased in HGF rats (21% p < 0.05). Microarray and quantitative rt-PCR analyses showed that the genes hgfac, rac 1, cdc42, and akt 1 were more than twofold up-regulated after HGF treatment.

CONCLUSION

HGF emerges as a growth factor that enhances intestinal adaptation. The future use of HGF may potentially reduce the requirement for PN in SBS patients.