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

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 develop...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 1996-07, Vol.137 (7), p.3131-3139
Main Authors: Otonkoski, T, Cirulli, V, Beattie, M, Mally, M I, Soto, G, Rubin, J S, Hayek, A
Format: Article
Language:English
Subjects:
Antibodies
Beta cells
c-Met protein
Cell culture
Cell differentiation
Cell growth
Cell proliferation
Clusters
Epithelial cells
Epithelium
Fetuses
Fibroblasts
Growth factors
Hepatocyte growth factor
Mesenchyme
mRNA
Pancreas
Protein folding
Scattering
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Summary: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.
ISSN:0013-7227
1945-7170
DOI:10.1210/endo.137.7.8770939