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Proc Natl Acad Sci U S A. 2011 Jun 7;108(23):9601-6. doi: 10.1073/pnas.1100981108. Epub 2011 May 18.

Nod-like receptor pyrin domain-containing protein 6 (NLRP6) controls epithelial self-renewal and colorectal carcinogenesis upon injury.

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1
University Lille Nord de France, F-59000 Lille, France.

Abstract

The colonic epithelium self-renews every 3 to 5 d, but our understanding of the underlying processes preserving wound healing from carcinogenesis remains incomplete. Here, we demonstrate that Nod-like receptor pyrin domain-containing protein 6 (NLRP6) suppresses inflammation and carcinogenesis by regulating tissue repair. NLRP6 was primarily produced by myofibroblasts within the stem-cell niche in the colon. Although NLRP6 expression was lowered in diseased colon, NLRP6-deficient mice were highly susceptible to experimental colitis. Upon injury, NLRP6 deficiency deregulated regeneration of the colonic mucosa and processes of epithelial proliferation and migration. Consistently, absence of NLRP6 accelerated colitis-associated tumor growth in mice. A gene-ontology analysis on a whole-genome expression profiling revealed a link between NLRP6 and self-renewal of the epithelium. Collectively, the integrity of the epithelial barrier is preserved by NLRP6 that may be manipulated to develop drugs capable of preventing adenoma formation in inflammatory bowel diseases.

PMID:
21593405
PMCID:
PMC3111299
DOI:
10.1073/pnas.1100981108
[Indexed for MEDLINE]
Free PMC Article

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