HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR HAS INSULINOTROPIC ACTIVITY IN HUMAN FETAL PANCREATIC-CELLS
HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR HAS INSULINOTROPIC ACTIVITY IN HUMAN FETAL PANCREATIC-CELLS
复制标题
DOI：
10.2337/diabetes.43.7.947
复制
发表时间：
1994-07-01
期刊：
影响因子：
7.7
通讯作者：
HAYEK, A
中科院分区：
文献类型：
--
作者：
OTONKOSKI, T;BEATTIE, GM;HAYEK, A
胎儿间充质源性因子可能在胰岛发育和生长中起重要作用。我们已经使用人胎儿胰腺组织的原代培养物来鉴定具有形态发生、促有丝分裂和促胰岛素活性的生长因子。在6天的培养过程中，肝细胞生长因子/分散因子（HGF/SF）、碱性成纤维细胞生长因子（FGF）-2刺激胰岛样细胞簇（ICC）的形成，并在较小程度上刺激角质形成细胞生长因子（FGF-7）和胰岛素样生长因子-II（IGF-II）。与此相反，转化生长因子-β（TGF-β）有很强的抑制作用，在HGF/SF刺激过程中形成的ICC主要由上皮细胞组成，而FGF-2诱导的ICC主要是非上皮细胞。此外，虽然FGF-2和HGF/SF都增加了培养物的总胰岛素含量，但只有HGF/SF增加了每个DNA的胰岛素含量。定量分析显示，HGF/SF刺激胰岛素阳性细胞比例增加2.3倍，复制β细胞数量增加3倍。阻断IGF-I受体可抑制ICC的形成，但不影响其胰岛素含量。免疫中和TGF-β导致细胞生长和胰岛素含量增加，表明模型系统中存在内源性抑制性TGF-β活性。我们的研究结果表明，HGF/SF可能是一个重要的组成部分，胎儿间充质衍生的因子负责胰岛发育。HGF/SF也可能被证明对支持胰岛细胞的体外生长有价值。
Fetal mesenchyme-derived factors are likely to play an important role in pancreatic islet development and growth. We have used primary cultures of human fetal pancreatic tissue to identify growth factors that have morphogenic, mitogenic, and insulinotropic activity. The formation of islet-like cell clusters (ICCs) during a 6-day culture was stimulated two- to threefold by hepatocyte growth factor/scatter factor (HGF/SF), basic fibroblast growth factor (FGF)-2, and to a lesser extent by keratinocyte growth factor (FGF-7) and insulin-like growth factor-II (IGF-II). In contrast, transforming growth factor-beta (TGF-beta) had a strong inhibitory effect, The ICCs formed during HGF/SF stimulation consisted mainly of epithelial cells, whereas FGF-2-induced ICCs were predominantly nonepithelial. Furthermore, although both FGF-2 and HGF/SF increased the total insulin content of the cultures, only HGF/SF increased the insulin content per DNA. Quantitatively, HGF/SF stimulated a 2.3-fold increase in the proportion of insulin-positive cells and a 3-fold higher number of replicating beta-cells. Blocking of the IGF-I receptor inhibited ICC formation but did not affect their insulin content. Immunoneutralizing TGF-beta resulted in increased cell growth and insulin content, indicating the presence of an endogenous inhibitory TGF-beta activity in the model system. Our results suggest that HGF/SF may be an important component of the fetal mesenchyme-derived factors responsible for pancreatic islet development. HGF/SF also may prove valuable for supporting the in vitro growth of islet cells.