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

Abstract

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&#xa0;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&#x2009;<&#x2009;0.05 and 27%, p&#x2009;<&#x2009;0.05 respectively).&#xa0;Enterocyte proliferation was also significantly increased in HGF rats (21% p&#x2009;<&#x2009;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.