Differential autocrine regulation of intestine epithelial cell proliferation and differentiation by insulin-like growth factor (IGF) system components
Differential autocrine regulation of intestine epithelial cell proliferation and differentiation by insulin-like growth factor (IGF) system components
复制标题
DOI：
10.1055/s-2007-978705
复制
发表时间：
1999-02-01
影响因子：
2.2
通讯作者：
Jungwirth, RJ
中科院分区：
文献类型：
--
作者：
Jehle, PM;Fussgaenger, RD;Jungwirth, RJ
调节肠上皮细胞更新的机制尚不完全清楚。本研究旨在通过比较快速生长的隐窝细胞 (IEC-6) 和分化的肠上皮细胞 (CaCo-2) 来表征自分泌 IGF 系统成分在肠上皮细胞增殖和分化中的作用。 IGF-I、IGF-II 和 IGFBP-1 至 -3 的自分泌释放通过特异性 RIA 和蛋白质配体印迹测定。此外，还研究了胰岛素、IGF-I 和 IGF-II 的结合和生长促进活性。通过测量刷状缘酶碱性磷酸酶和蔗糖酶来评估肠细胞分化。在 IEC-6 生长过程中，IGF-1 和-II 的自分泌释放增加，而 IGFBP-2 水平下降。可以检测到 IGF-I 和 IGF-II 的特异性受体，但不能检测到胰岛素。 IGF-I 刺激 IEC-6 细胞增殖的能力比胰岛素强 100 倍。相反，CaCo-2细胞显示出比ICF-I/-II更高的胰岛素结合并且不释放ICF-I。从CaCo2细胞增殖转向分化时，测量到IGF-II（10倍）、IGFBP-1（2.5倍）、IGFBP-2（3倍）和IGFBP-3（6倍）的分泌显着增加。我们的数据表明 IGF 系统成分差异调节肠细胞增殖和分化。
The mechanisms which regulate cell turnover in the intestinal epithelium are incompletely understood. The present study was performed to characterize the role of autocrine IGF system components in intestine epithelial cell proliferation and differentiation comparing rapidly growing crypt cells (IEC-6) with differentiating enterocytes (CaCo-2). The autocrine release of IGF-I, IGF-II and IGFBP-1 through -3 was determined by specific RIAs and western ligand blotting. In addition, binding and growth-promoting activity of insulin, IGF-I and IGF-II was investigated. Enterocytic differentiation was assessed by measuring the brush-border enzymes alkaline phosphatase and sucrase. During IEC-6 growth, the autocrine release of IGF-l and -II increased, whereas IGFBP-2 levels decreased. Specific receptors for IGF-I and IGF-II but not insulin could be detected. IGF-I was 100-fold more potent than insulin to stimulate IEC-6 cell proliferation. In contrast, CaCo-2 cells revealed higher binding of insulin than ICF-I/-II and no release of ICF-I. At switch from CaCo2 cell proliferation to differentiation a marked increase in the secretion of IGF-II (10-fold), IGFBP-1 (2.5-fold), IGFBP-2 (3-fold), and IGFBP-3 (6-fold) was measured. Our data indicate that IGF system components differentially modulate enterocytic cell proliferation and differentiation.