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生长因子对培养的人肠肌生长的自分泌调节。

Autocrine regulation of growth in cultured human intestinal muscle by growth factors.

作者信息

Kuemmerle J F

机构信息

Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA.

出版信息

Gastroenterology. 1997 Sep;113(3):817-24. doi: 10.1016/s0016-5085(97)70176-8.

DOI:10.1016/s0016-5085(97)70176-8
PMID:9287973
Abstract

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 rapid 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 [3H]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.

摘要

背景与目的

转化生长因子(TGF)-α、胰岛素样生长因子(IGF)-I和TGF-β1在体内由肠道平滑肌表达。本研究的目的是确定这些生长因子是否由培养的人肠道肌肉细胞产生,并确定它们在调节生长中的作用。

方法

在培养的不同时间点检查肌肉细胞:快速生长期间(第3天)、汇合时(第7天)和汇合后(第14天)。通过放射免疫测定法或酶联免疫吸附测定法测量生长因子的产生。通过[3H]胸苷掺入测量生长。

结果

前体TGF-α和TGF-α的产生(分别为1550±100和1260±150 pg/mg蛋白质)以及游离IGF-I(86.2±23.7 ng/mg蛋白质)在快速生长期间最高,在培养后期降低3至40倍。可溶性和潜伏性TGF-β1的产生在汇合后细胞中最高(分别为280±74和4320±610 pg/mg蛋白质),在培养早期降低4至7倍。TGF-α和IGF-I在快速生长的细胞中引起浓度依赖性的生长刺激。TGF-β1主要在汇合后细胞中引起浓度依赖性的生长抑制。针对TGF-α或IGF-I的中和抗体抑制生长,而针对TGF-β的中和抗体增强生长。

结论

人肠道肌肉细胞以时间依赖性的相互方式产生TGF-α、IGF-I和TGF-β1,这与它们对生长的影响相似。

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