The Myc 3' Wnt responsive element regulates neutrophil recruitment after acute colonic injury in mice.

The Myc 3' Wnt responsive element regulates neutrophil recruitment after acute colonic injury in mice.
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DOI:
10.1007/s10620-013-2686-x
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发表时间:
2013-10
影响因子:
3.1
通讯作者:
Yochum, Gregory S.
Yochum, Gregory S.
中科院分区:
医学3区
文献类型:
--
作者:
Konsavage, Wesley M., Jr.;Roper, Jennifer N.;Ishmael, Faoud T.;Yochum, Gregory S.

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Wnt/β-catenin途径调节肠发育、稳态和损伤后的再生。Wnt/β-catenin信号通过Myc 3′ Wnt应答DNA元件(Myc 3′ WRE)激活c-Myc原癌基因(Myc)的表达来驱动肠增殖。在先前的研究中,我们发现小鼠中Myc 3′ WRE的缺失导致结肠中MYC表达增加和细胞增殖增加。当被葡聚糖硫酸钠(DSS)损伤时,Myc 3′ WRE−/−结肠细胞的增殖能力增加导致与野生型(WT)小鼠相比更快的恢复。在这项研究中,我们没有检查免疫系统参与结肠再生。描述DSS诱导的结肠损伤期间和之后Myc 3′ WRE−/−和WT小鼠的先天免疫应答。将2.5%DSS在其饮用水中喂食小鼠五天以诱导结肠损伤,然后恢复正常水两天或四天以恢复。制备结肠切片,通过免疫组织化学分析中性粒细胞和巨噬细胞。通过用结肠裂解物探测细胞因子阵列来分析细胞因子和趋化因子水平。与WT小鼠相比,DSS损伤后Myc 3′ WRE−/−小鼠结肠粘膜和粘膜下层的白细胞浸润增加。在受损的Myc 3′ WRE−/−结肠中,活化的中性粒细胞水平显著升高,中性粒细胞趋化因子C5/C5 a、CXCL 1和CXCL 2的水平也是如此。Myc 3′ WRE调节中性粒细胞浸润到DSS损伤的结肠中。
The Wnt/β-catenin pathway regulates intestinal development, homeostasis, and regeneration after injury. Wnt/β-catenin signaling drives intestinal proliferation by activating expression of the c-Myc proto-oncogene (Myc) through the Myc 3′ Wnt responsive DNA element (Myc 3′ WRE). In a previous study, we found that deletion of the Myc 3′ WRE in mice caused increased MYC expression and increased cellular proliferation in the colon. When damaged by dextran sodium sulfate (DSS), the increased proliferative capacity of Myc 3′ WRE−/− colonocytes resulted in a more rapid recovery compared with wild-type (WT) mice. In that study, we did not examine involvement of the immune system in colonic regeneration. To characterize the innate immune response in Myc 3′ WRE−/− and WT mice during and after DSS-induced colonic injury. Mice were fed 2.5 % DSS in their drinking water for five days to induce colonic damage and were then returned to normal water for two or four days to recover. Colonic sections were prepared and neutrophils and macrophages were analyzed by immunohistochemistry. Cytokine and chemokine levels were analyzed by probing a cytokine array with colonic lysates. In comparison with WT mice, there was enhanced leukocyte infiltration into the colonic mucosal and submucosal layers of Myc 3′ WRE−/− mice after DSS damage. Levels of activated neutrophils were substantially increased in damaged Myc 3′ WRE−/− colons as were levels of the neutrophil chemoattractants C5/C5a, CXCL1, and CXCL2. The Myc 3′ WRE regulates neutrophil infiltration into DSS-damaged colons.
DOI: 10.1124/jpet.108.145862
发表时间: 2009-04-01
影响因子: 3.5
作者:
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发表时间: 2011-09-16
期刊: Cell
影响因子: 64.5
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发表时间: 1998-09-04
期刊: SCIENCE
影响因子: 56.9
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