Altered intestinal epithelial homeostasis in mice with intestine-specific deletion of the Krüppel-like factor 4 gene.
Altered intestinal epithelial homeostasis in mice with intestine-specific deletion of the Krüppel-like factor 4 gene.
复制标题
DOI：
10.1016/j.ydbio.2010.11.001
复制
发表时间：
2011-01-15
影响因子：
2.7
通讯作者：
Yang VW
中科院分区：
文献类型：
--
作者：
Ghaleb AM;McConnell BB;Kaestner KH;Yang VW
锌指转录因子Krüppel-like factor4(KLF4)在肠道有丝分裂后分化的上皮细胞中表达，对肠道肿瘤的发生具有抑制作用。在这里，我们报告了KLF4在维持肠上皮细胞动态平衡中的作用。从肠上皮有条件地去除KLF4基因的小鼠是存活的。然而，突变小鼠的小肠上皮细胞的增殖率和移行率都有所增加。此外，刷状缘碱性磷酸酶在小肠中的表达减少，导致潘氏细胞定位错误。在突变小鼠的结肠中，分化标记物碳酸氢酶-1降低，杯状细胞分化失败。从机制上讲，从肠道中删除KLF4导致Wnt途径中的基因普遍激活，编码分化调节基因的全球表达减少。综上所述，这些数据为KLF4在调节出生后肠上皮细胞的增殖、迁移、分化和定位中的功能提供了新的见解，并证明了KLF4在体内维持正常的肠上皮动态平衡中的重要作用。
The zinc finger transcription factor, Krüppel-like factor 4 (KLF4), is expressed in the post-mitotic, differentiated epithelial cells lining the intestinal tract and exhibits a tumor suppressive effect on intestinal tumorigenesis. Here we report a role for KLF4 in maintaining homeostasis of intestinal epithelial cells. Mice with conditional ablation of the Klf4 gene from the intestinal epithelium were viable. However, both the rates of proliferation and migration of epithelial cells were increased in the small intestine of mutant mice. In addition, the brush-border alkaline phosphatase was reduced as was expression of ephrine-B1 in the small intestine, resulting in mispositioning of Paneth cells. In the colon of mutant mice, there was a reduction of the differentiation marker, carbonic anhydrase-1, and failure of differentiation of goblet cells. Mechanistically, deletion of Klf4 from the intestine resulted in a general activation of genes in the Wnt pathway and a global reduction in expression of genes encoding regulators of differentiation. Taken together, these data provide new insights into the function of KLF4 in regulating postnatal proliferation, migration, differentiation, and positioning of intestinal epithelial cells and demonstrate an essential role for KLF4 in maintaining normal intestinal epithelial homeostasis in vivo.
登录
查看更多内容
影响因子：
1.9
作者：
Chutkan, RK
通讯作者：
Chutkan, RK
DOI：
10.1016/s0006-291x(03)01356-1
发表时间：
2003-08-22
影响因子：
3.1
作者：
Ohnishi, S;Ohnami, S;Yoshida, T
通讯作者：
Yoshida, T
DOI：
10.1152/ajpgi.00203.2003
发表时间：
2004-01-01
影响因子：
4.5
作者：
Hinnebusch, BF;Siddique, A;Hodin, RA
通讯作者：
Hodin, RA
影响因子：
4.8
作者：
Madison, BB;Dunbar, L;Gumucio, DL
通讯作者：
Gumucio, DL
影响因子：
11.4
作者：
MAUNOURY, R;ROBINE, S;LOUVARD, D
通讯作者：
LOUVARD, D