Autocrine regulation of growth in cultured human intestinal muscle by growth factors
Autocrine regulation of growth in cultured human intestinal muscle by growth factors
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DOI：
10.1016/s0016-5085(97)70176-8
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发表时间：
1997-09-01
期刊：
影响因子：
29.4
通讯作者：
Kuemmerle, JF
中科院分区：
文献类型：
--
作者：
Kuemmerle, JF
背景和目标：转化生长因子（TGF）-α、胰岛素样生长因子（IGF）-I和TGF-β 1在体内由肠平滑肌表达。本研究的目的是确定这些生长因子是否由培养的人肠肌细胞产生，并确定它们在调节生长中的作用。方法：在培养的不同时间检查肌细胞：在vapid生长期间（第3天），在汇合时（第7天），和汇合后（第14天）。通过放射免疫分析或酶联免疫吸附试验测定生长因子的产生。从[H-3]胸苷掺入测量生长。结果如下：pro-TGF-α和TGF-α（分别为1550 +/- 100和1260 +/- 150 pg/mg蛋白质）和游离IGF-I（86.2 +/- 23.7 ng/mg蛋白质）的产生在快速生长期间最高，并且在培养后期降低3-40倍。融合后细胞中可溶性和潜伏性TGF-β 1的产量最高（分别为280 +/- 74和4320 +/- 610 pg/mg蛋白），而培养早期的产量低4-7倍。TGF-α和IGF-I在快速生长的细胞中引起浓度依赖性生长刺激。TGF-β 1主要在融合后细胞中引起浓度依赖性生长抑制。TGF-α或IGF-I的中和抗体抑制生长，TGF-β的中和抗体增强生长。结论：人类肠肌细胞以时间依赖性的相互方式产生TGF-α、IGF-I和TGF-β 1，这与它们对生长的影响平行。
Background & Aims: Transforming growth factor (TGF)-alpha, insulin-like growth factor (IGF)-I, and TGF-beta 1 are expressed in vivo by intestinal smooth muscle. The aim of this study was to determine whether these growth factors were produced by human intestinal muscle cells in culture and to identify their roles in regulating growth. Methods: Muscle cells were examined at various times in culture: during vapid growth (day 3), at confluence (day 7), and after confluence (day 14). Growth factor production was measured by radioimmunoassay or enzyme-linked immunosorbent assay. Growth was measured from [H-3]thymidine incorporation. Results: Production of pro-TGF-alpha and TGF-alpha (1550 +/- 100 and 1260 +/- 150 pg/mg protein, respectively) and free IGF-I (86.2 +/- 23.7 ng/mg protein) was highest during rapid growth and 3-40-fold lower later in culture. Production of soluble and latent TGF-beta 1 was highest in postconfluent cells (280 +/- 74 and 4320 +/- 610 pg/mg protein, respectively) and 4-7 fold lower earlier in culture. TGF-alpha and IGF-I caused concentration-dependent stimulation of growth in rapidly growing cells. TGF-beta 1 caused concentration-dependent inhibition of growth predominantly in postconfluent cells. Neutralizing antibodies to TGF-alpha or IGF-I inhibited growth and neutralizing antibody to TGF-beta augmented growth. Conclusions: Human intestinal muscle cells produce TGF-alpha, IGF-I, and TGF-beta 1 in a time-dependent reciprocal fashion that parallels their effects on growth.