Kruppel-like factor 5 mediates transmissible murine colonic hyperplasia caused by Citrobacter rodentium infection
Kruppel-like factor 5 mediates transmissible murine colonic hyperplasia caused by Citrobacter rodentium infection
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DOI：
10.1053/j.gastro.2008.01.013
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发表时间：
2008-04-01
期刊：
影响因子：
29.4
通讯作者：
Yang, Vincent W.
中科院分区：
文献类型：
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作者：
McConnell, Beth B.;Klapproth, Jan-Michael A.;Yang, Vincent W.
背景和目标：Kruppel样因子5（KLF 5）是一种在肠上皮细胞的增殖隐窝细胞中高度表达的转录因子。KLF 5在体外具有促增殖作用，并由促有丝分裂和应激刺激诱导。为了确定KLF 5是否参与介导体内肠应激的增殖反应，我们研究了其在由细菌啮齿类柠檬酸杆菌（Citrobacter rodentium）在小鼠结肠定殖引发的小鼠传染性小鼠结肠增生模型中的功能。方法：从携带Klf 5基因插入破坏的胚胎干细胞产生杂合Klf 5敲除（Klf 5（+/-））小鼠。Klf 5（+/-）小鼠或野生型（WT）同窝小鼠经口灌胃感染啮齿类梭菌。在感染后的不同时间点，处死小鼠并收获远端结肠。结肠隐窝高度从用H&E染色的切片形态测定。使用抗Klf 5和增殖标志物Ki 67的抗体通过免疫荧光对冷冻组织进行染色，以确定Klf 5表达和每个隐窝的增殖细胞数。结果如下：感染啮齿类梭菌的WT小鼠在感染后14天结肠隐窝高度增加了2倍，并伴随着Klf 5表达增加了1.7倍。Klf（+/-）小鼠的感染显示Klf 5表达的减弱诱导，并且与WT同窝小鼠相比，Klf 5（+/-）动物中对啮齿类衣原体的过度增殖反应降低。结论：Klf 5是大肠菌感染后结肠腺细胞增殖的关键因子。
Background & Aims: Kruppel-like factor 5 (KLF5) is a transcription factor that is highly expressed in proliferating crypt cells of the intestinal epithelium. KLF5 has a pro-proliferative effect in vitro and is induced by mitogenic and stress stimuli. To determine whether KLF5 is involved in mediating proliferative responses to intestinal stressors in vivo, we examined its function in a mouse model of transmissible murine colonic hyperplasia triggered by colonization of the mouse colon by the bacteria Citrobacter rodentium. Methods: Heterozygous Klf5 knockout (Klf5(+/-)) mice were generated from embryonic stem cells carrying an insertional disruption of the Klf5 gene. Klf5(+/-) mice or wild-type (WT) littermates were infected with C rodentium by oral gavage. At various time points postinfection, mice were killed and distal colons were harvested. Colonic crypt heights were determined morphometrically from sections stained with H&E. Frozen tissues were stained by immunofluorescence using antibodies against Klf5 and the proliferation marker, Ki67, to determine Klf5 expression and numbers of proliferating cells per crypt. Results: Infection of WT mice with C rodentium resulted in a 2-fold increase in colonic crypt heights at 14 clays postinfection and was accompanied by a 1.7-fold increase in Klf5 expression. Infection of Klf(+/-) mice showed an attenuated induction of Klf5 expression, and hyperproliferative responses to C rodentium were reduced in the Klf5(+/-) animals as compared with WT littermates. Conclusion: Our study shows that Klf5 is a key mediator of crypt cell proliferation in the colon in response to pathogenic bacterial infection.