Evidence for the involvement of NOD2 in regulating colonic epithelial cell growth and survival

Sheena M. Cruickshank, Louise Wakenshaw, John Cardone, Peter D. Howdle, Peter J. Murray, Simon R. Carding

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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. © 2008 The WJG Press. All rights reserved.
    Original languageEnglish
    Pages (from-to)5834-5841
    Number of pages7
    JournalWorld Journal of Gastroenterology
    Volume14
    Issue number38
    DOIs
    Publication statusPublished - 14 Oct 2008

    Keywords

    • Colon
    • Epithelial cells
    • Growth
    • NOD2

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