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作者机构：Molecular and Cellular Biology University of Leeds Leeds LS2 9JT United Kingdom Faculty of Life Sciences University of Manchester Manchester M13 9PT United Kingdom Institute of Molecular and Cellular Biology University of Leeds Leeds LS2 9JT United Kingdom The Institute of Food Research Norwich Research Park Norwich NR4 7UA United Kingdom Institute of Molecular and Cellular Biology University of Leeds Leeds LS2 9JT United Kingdom Section of Medicine Surgery & Anaesthesia Leeds Institute of Molecular Medicine University of Leeds Leeds LS2 9JT United Kingdom Department of Infectious Diseases St. Jude Children's Research Hospital Memphis TN 38105 United States
出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)
年 卷 期：2008年第14卷第38期
页 面：5834-5841页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：in part) Grants from Action Medical Research (SRC, SMC The Leeds Teaching Hospitals Charitable Foundation (SRC and PH), NIH (PJM) The European Union "Leonardo da Vinci" Scholarship Program (JC) BBSRC sponsored postgraduate studentship (LW) The American Lebanese Syrian Associated Charities (PJM)
摘 要：AIM: To investigate the function of NOD2 in colonic epithelial cells (CEC). METHODS: A combination of in vivo and in vitro analyses of epithelial 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.
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