A role for hepatocyte growth factor/scatter factor in fetal mesenchyme-induced pancreatic beta-cell growth

Endocrinology. 1996 Jul;137(7):3131-9. doi: 10.1210/endo.137.7.8770939.

Abstract

We have investigated the role of hepatocyte growth factor/scatter factor (HGF/SF) in the growth and/or differentiation of pancreatic islet beta-cells. We found that in the human fetal pancreas immunoreactive HGF/SF receptor (c-met proto-oncogene product) is preferentially associated with the developing beta-cells. In the adult pancreas, c-met messenger RNA is highly enriched in the islets and the immunoreactive protein is also restricted to the islet beta-cells. HGF/SF messenger RNA content of fetal pancreas-derived fibroblasts is more than 10-fold higher than that of adult fibroblasts. Culture of human fetal pancreatic epithelial cells in conditioned medium from the fetal pancreatic fibroblasts caused a 2.4-fold stimulation of the formation of islet-like cell clusters that was due to both mitogenic and morphogenic effects. Beta-cell proliferation in the cell clusters was stimulated 3.5-fold by the conditioned medium, and this was associated with a marked decrease in insulin content. All of the effects of the conditioned medium were blocked by anti-HGF/SF antibody. Specificity was confirmed by overriding the blocking effect of the antibody with excess recombinant HGF/SF. Conditioned medium from adult pancreatic fibroblasts stimulated islet-like cell cluster formation only slightly, and did not affect beta-cell replication. These results suggest that HGF/SF secreted by fetal fibroblasts is mitogenic to beta-cells. Taken together, our findings indicate an important role for HGF/SF in fetal mesenchyme-induced pancreatic beta-cell growth.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Analysis of Variance
  • Cell Division
  • Cells, Cultured
  • Culture Media, Conditioned
  • Fetus
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Fluorescent Antibody Technique
  • Gestational Age
  • Glucagon / analysis
  • Glucagon / biosynthesis
  • Hepatocyte Growth Factor / biosynthesis
  • Hepatocyte Growth Factor / pharmacology*
  • Hepatocyte Growth Factor / physiology*
  • Humans
  • Insulin / analysis
  • Insulin / biosynthesis
  • Islets of Langerhans / cytology
  • Islets of Langerhans / embryology
  • Islets of Langerhans / physiology*
  • Mesoderm / physiology*
  • Microscopy, Confocal
  • Proto-Oncogene Proteins c-met
  • RNA, Messenger / biosynthesis
  • Receptor Protein-Tyrosine Kinases / biosynthesis*
  • Recombinant Proteins / pharmacology
  • Transcription, Genetic

Substances

  • Culture Media, Conditioned
  • Insulin
  • RNA, Messenger
  • Recombinant Proteins
  • Hepatocyte Growth Factor
  • Glucagon
  • Proto-Oncogene Proteins c-met
  • Receptor Protein-Tyrosine Kinases