Evidence for the involvement of NOD2 in regulating colonic epithelial cell growth and survival
Evidence for the involvement of NOD2 in regulating colonic epithelial cell growth and survival
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DOI：
10.3748/wjg.14.5834
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发表时间：
2008-10-14
影响因子：
4.3
通讯作者：
Carding, Simon R.
中科院分区：
文献类型：
--
作者：
Cruickshank, Sheena M.;Wakenshaw, Louise;Carding, Simon R.
目的：探讨NOD 2在结肠上皮细胞（CEC）中的作用。方法：使用了在存在和不存在功能性NOD 2蛋白的情况下以及响应肠沙门氏菌感染的上皮细胞更新的体内和体外分析的组合。利用shRNA干扰技术研究NOD 2基因表达下调对大肠癌细胞生长和存活的影响。结果：在结肠粘膜中，NOD 2表达水平最高的是增殖的隐窝上皮细胞。胞壁酰二肽（MDP）是NOD 2识别的多肽，在体外可促进CEC的生长。相反，NOD 2缺陷的CEC的生长受到损害。在Nod 2（-/-）小鼠中，体内CEC增殖也减少，凋亡增加，这在肠道沙门氏菌感染后也是明显的。此外，通过shRNA干扰中和人结肠癌细胞中NOD 2 mRNA的表达，由于细胞凋亡水平增加，导致存活率降低。结论：NOD 2蛋白参与了CEC的生长和存活。CD病例中CEC增殖缺陷可能导致肠道稳态破坏和过度炎症的潜在病理学。(C)2008年，WIG出版社。All rights reserved.
AIM: To investigate the function of NOD2 in colonic epithelial cells (CEC). METHODS: A combination of in vivo and in vitro analyses of epithelia[ cell turnover in the presence and absence of a functional NOD2 protein and, in response to enteric Salmonella typhimurium infection, were used. shRNA interference was also used to investigate the consequences of knocking down NOD2 gene expression on the growth and survival of colorectal carcinoma cell lines. RESULTS: In the colonic mucosa the highest levels of NOD2 expression were in proliferating crypt epithelial cells. Muramyl dipeptide (MDP), that is recognized by NOD2, promoted CEC growth in vitro. By contrast, the growth of NOD2-deficient CECs was impaired. in vivo CEC proliferation was also reduced and apoptosis increased in Nod2(-/-) mice, which were also evident following enteric Salmonella infection. Furthermore, neutralization of NOD2 mRNA expression in human colonic carcinoma cells by shRNA interference resulted in decreased survival due to increased levels of apoptosis. CONCLUSION: These findings are consistent with the involvement of NOD2 protein in promoting CEC growth and survival. Defects in proliferation by CECs in cases of CD may contribute to the underlying pathology of disrupted intestinal homeostasis and excessive inflammation. (C) 2008 The WIG Press. All rights reserved.