A role for hepatocyte growth factor/scatter factor in fetal mesenchyme-induced pancreatic beta-cell growth.
A role for hepatocyte growth factor/scatter factor in fetal mesenchyme-induced pancreatic beta-cell growth.
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DOI：
10.1210/endo.137.7.8770939
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发表时间：
1996-07
期刊：
影响因子：
4.8
通讯作者：
T. Otonkoski;Vincenzo Cirulli;Michael S. Beattie;M. Mally;Gabriel E. Soto;Jeffrey Rubin;A. Hayek-A.-Haye
中科院分区：
文献类型：
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作者：
T. Otonkoski;Vincenzo Cirulli;Michael S. Beattie;M. Mally;Gabriel E. Soto;Jeffrey Rubin;A. Hayek-A.-Haye
我们研究了肝细胞生长因子/分散因子（HGF/SF）在胰岛β细胞生长和/或分化中的作用。我们发现，在人胎儿胰腺免疫反应性HGF/SF受体（c-met原癌基因产物）优先与发育中的β细胞相关。在成人胰腺中，c-met信使RNA在胰岛中高度富集，并且免疫反应性蛋白也限于胰岛β细胞。胎儿胰腺成纤维细胞的HGF/SF信使RNA含量比成人成纤维细胞高10倍以上。在来自胎儿胰腺成纤维细胞的条件培养基中培养人胎儿胰腺上皮细胞引起胰岛样细胞簇形成的2.4倍刺激，这是由于促有丝分裂和形态发生效应。条件培养基刺激细胞簇中的β细胞增殖3.5倍，这与胰岛素含量显著降低有关。抗HGF/SF抗体可阻断条件培养液的上述作用。通过用过量重组HGF/SF覆盖抗体的阻断作用来确认特异性。成人胰腺成纤维细胞的条件培养基刺激胰岛样细胞簇的形成只有轻微的，并没有影响β细胞的复制。这些结果表明，胎儿成纤维细胞分泌的HGF/SF对β细胞具有促有丝分裂作用。总而言之，我们的研究结果表明HGF/SF在胎儿间充质诱导的胰腺β细胞生长中发挥重要作用。
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.