Hepatocyte growth factor increases glucagon immunoreactivity in jejunal cells during intestinal adaptation

BackgroundThe administration of hepatocyte growth factor (HGF) during intestinal adaptation is known to enhance intestinal adaptation. Glucagon has also been implicated as a potential mediator of intestinal adaptation. Previous studies have shown that HGF and glucagon synergistically increase the proliferation of hepatocytes. HGF has also been shown to be preferentially expressed within the glucagon-positive cells of the pancreas, possibly indicating a paracrine or endocrine effect of HGF on glucagon. This study was designed to determine if HGF stimulation in the small intestine during intestinal adaptation influenced mucosal glucagon expression.MethodsAdult male Sprague-Dawley rats were randomized to either a 70% massive small bowel resection group (MSBR) or an HGF-treated MSBR group (MSBR-HGF). Seven days after surgery, HGF was administered intravenously at 150 μg/kg per day for 14 days. At day 21, the ileal and jejunal mucosa was harvested. The RAE 230A GeneChip (Affymetrix, Santa Clara, Calif) and MAS5 software were used to determine alterations in gene expression in the small intestine mucosa. Immunofluorescent staining of the ileal and jejunal mucosa using an antiglucagon antibody was performed and evaluated qualitatively.ResultsThe MSBR-HGF group had significantly greater protein and DNA content (P < .05) than the MSBR group. Glucagon gene expression in the MSBR-HGF group was decreased compared with the MSBR group, and immunohistostaining for glucagon in the ileum revealed no difference in intensity between the 2 groups. However, the jejunal MSBR-HGF group demonstrated significantly greater glucagon immunoreactivity than the jejunal MSBR group.ConclusionOur data suggest that the HGF-induced increase in glucagon availability is disassociated from glucagon gene up-regulation. Thus, HGF may not only enhance intestinal adaptation directly, but also indirectly by increasing the “local” availability of other growth factors in the absence of their gene up-regulation.