Enhancement of intestinal adaptation by hepatocyte growth factor

Abstract

Background/Purpose: Hepatocyte growth factor (HGF) was originally shown to enhance hepatocyte DNA synthesis. Recently, the expression of HGF and its receptor (c-met) were observed in the intestinal tract. In a previous study, we demonstrated that HGF can increase normal rat intestinal epithelial mass and function in vivo. This study was designed to determine if HGF, given either systemically or luminally, can enhance intestinal epithelial mass and function beyond the normal adaptive response after massive small bowel resection. Methods: Twenty young adult male Sprague-Dawley rats underwent an 80% small bowel resection. Seven days after resection, systemic infusion (via the jugular vein) or luminal perfusion (via the jejunum) were performed using subcutaneously placed osmotic minipumps. The rats were divided into four groups: group 1, systemic saline, (control, n = 5); group 2, systemic HGF at 150 μg/kg/d (n = 5); group 3, luminal saline, (control, n = 5); and group 4, luminal HGF at 75 μg/kg/d (n = 5). After a 14-day infusion, [C 14] galactose and [C 14] glycine absorption (μmol/cm 2 intestine), mucosal DNA content (μg/mg mucosa) and protein content (μg/mg mucosa) were measured in the remaining small intestine of each rat. Results: Systemic infusion of HGF increased galactose absorption 68% ( P < .05), glycine absorption 57% ( P < .05), DNA content 17% ( P < .01), and protein content 57% ( P < .01), when compared with the appropriate control. Luminal perfusion of HGF also increased galactose absorption 114% ( P < .01), glycine absorption 126% ( P < .01), DNA content 32% ( P < .01), and protein content 45% ( P < .01), when compared with the appropriate control. Conclusions: These data demonstrate for the first time that HGF can significantly enhance intestinal epithelial cell function and mucosal mass beyond the normal adaptive response. Luminal administration appeared to produce a greater response when compared with systemic administration but was significant only for galactose absorption ( P < .05). HGF may be clinically useful in patients with short bowel syndrome.