Glucocorticoids have pleiotropic effects on small intestinal crypt cells

Glucocorticoids have pleiotropic effects on small intestinal crypt cells
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DOI:
10.1152/ajpgi.1999.277.5.g1027
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发表时间:
1999-11-01
影响因子:
4.5
通讯作者:
Podolsky, DK
Podolsky, DK
中科院分区:
医学2区
文献类型:
--
作者:
Quaroni, A;Tian, JQ;Podolsky, DK

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糖皮质激素长期以来一直被认为可以加速肠道的成熟,但解释其在上皮中生理功能的分子机制仍然缺乏特征。使用大鼠肠上皮细胞系(IEC-B,IEC-17和IEC-18)作为模型,我们已经确定了糖皮质激素受体在隐窝细胞和记录显着的形态,超微结构和功能的改变,这些激素诱导的肠细胞。它们包括生长停滞、紧密连接的形成、细长微绒毛的出现、内质网和反式高尔基体网络的重组以及细胞周期调节蛋白细胞周期蛋白依赖性激酶6和p27(Kip 1)的下调。这些影响与吸收绒毛细胞生理功能中重要的多个基因的激活或调节一致,但可能不直接参与细胞分化的诱导。
Glucocorticoids have long been known to accelerate maturation of the intestinal tract, but the molecular mechanisms that account for their physiological function in the epithelium remain poorly characterized. Using rat intestinal epithelial cell lines (IEC-B, IEC-17, and IEC-18) as models, we have characterized glucocorticoid receptors in crypt cells and documented striking morphological, ultrastructural, and functional alterations induced by these hormones in intestinal cells. They include arrest of growth, formation of tight junctions, appearance of long, slender microvilli, reorganization of the endoplasmic reticulum and trans-Golgi network, and downregulation of the cell cycle regulatory proteins cyclin-dependent kinase 6 and p27(Kip1). These effects are consistent with the activation or modulation of multiple genes important in the physiological function of absorptive villous cells but are probably not directly involved in the induction of cell differentiation.