Proliferative Effects of Glicentin on Human Intestinal Epithelial Cells
Proliferative Effects of Glicentin on Human Intestinal Epithelial Cells
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肠高血糖素对人肠上皮细胞的增殖作用
DOI：
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Y. Sanada
中科院分区：
文献类型：
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作者：
M. Chiba;Y. Yoshizawa;M. Yamaguchi;Y. Sanada
一些激素因素在各种疾病中的潜在治疗作用目前正在调查中。其中，肠高血糖素，包括已合成的作为小肠生长因子的甘草素。本研究旨在评价甘草素与其他几种肠道生长因子联合应用时的促增殖作用，并探讨其对肠上皮细胞增殖的调控机制。我们建立了一种无血清条件下测定重组人粘连蛋白对人小肠上皮细胞株(INT-407)营养活性的体外生物测定体系。无血清培养1d后，分别加入格列汀、EGF、IGF-I、12-O-十四酰佛波醇(TPA)、前列腺素E_1(PGE-1)、格列汀+EGF、格列汀+IGF-I、格列汀+TPA、格列汀+前列腺素E_1、10%胎牛血清(FCS)或不加生长因子。观察治疗后肠上皮细胞增殖和蛋白酪氨酸激酶活性变化。1)在10~10ƒ/m l剂量范围内，格列森汀具有明显的肠道营养作用，且在1ƒ/m l以下呈现平行的剂量-反应曲线，其最大营养活性与表皮生长因子和胰岛素样生长因子-I的作用相当。2)Glicentin与EGF、IGF-I和PGE1单独作用的营养效应比单独作用更强，相当于10%胎牛血清的作用。然而，在TPA长时间预处理下调蛋白激酶C后，Gleicentin未能表现出这种促增殖作用。3)Glicentin与这些细胞结合后，蛋白酪氨酸激酶(PTK)活性增加。这些结果表明，Gleicentin的肠道营养作用是通过PTK和蛋白激酶C的信号通路来调节的，这种细胞内信号通路可能是选择性促进上皮细胞生长的重要因素，某些生长因子与Gelicentin联合使用可能对肠功能不足的患者有好处。
The potential therapeutic role of a number of hormonal factors in a variety of diseases are currently being investigated. Among them, the enteroglucagons, including glicentin, which has been synthesized as a growth factor for the small intestine. This study was designed to evaluate the proliferative effect of glicentin when used with several other intestinal growth factors and to elucidate the regulating mechanism of this enterocyte proliferation by glicentin. We have established an in vitro bioassay system for determining the trophic activity of recombinant human glicentin on the human small-intestinal epithelial cell line (INT-407) under serum-free conditions. The cells were serumdeprived for 1 day, and then treated with either glicentin, EGF, IGF-I, 12-O-tetradecanoylphorbol (TPA) , prostaglandin E1 (PGE 1) , glicentin with EGF, glicentin with IGF-I, glicentin with TPA, glicentin with PGE1, 10% fetal bovine serum (FCS); or no growth factor. We investigated enterocyte proliferation and protein tyrosine kinese activity after treatment. 1) Glicentin demonstrated significant enterotrophic effects at doses ranging from 10 ng/ml to 10ƒÊg/ml, and also showed a parallel dose-response curve at doses of less than 1ƒÊg / ml. The maximum trophic activity of glicentin was equivalent to the effects of EGF and IGF-I. 2) Glicentin in combination with either EGF, IGF-I and PGE1 had greater trophic effects than acting alone, which were equivalent to the effect of 10% FCS. However, glicentin failed to demonstrate this proliferative effect after the down regulation of protein kinase C with prolonged pretreatment with TPA. 3) Glicentin binding to these cells resulted in an increase in protein tyrosin kinase (PTK) activity. These results suggest that the enterotrophic effects of glicentin are regulated by a signaling pathway through PTK and protein kinase C. This intracellular signaling pathway of glicentin may be an important factor in selectively enhancing epithelial cell growth, and certain growth factors in combination with glicentin may provide a benefit for patients with inadequate enteric function.
表皮生长因子和转化生长因子α诱导c-fos和c-myc原癌基因表达是不依赖于钙的。
DOI：
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发表时间：
1989
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Cutry,AF;Kinniburgh,AJ;Krabak,MJ;Hui,SW;Wenner,CE
通讯作者：
Wenner,CE
表皮生长因子对小肠谷氨酰胺转运的调节。
影响因子：
3.8
作者：
Salloum,RM;Stevens,BR;Schultz,GS;Souba,WW
通讯作者：
Souba,WW