Journal
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Volume 287, Issue 1, Pages G220-G227Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00498.2003
Keywords
host defense; inflammation; cellular proliferaton
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Funding
- NHLBI NIH HHS [HL 60033] Funding Source: Medline
- NIDDK NIH HHS [DK 42086, DK 47662, DK 35932] Funding Source: Medline
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The mucosal lining of the human intestine is constantly bathed in a milieu of commensal gut flora, the vast majority of these being nonpathogenic microorganisms. Here, we demonstrate that microbial-epithelial cell interactions not only affect proinflammatory pathways but also influence beta-catenin signaling, a key component in regulating epithelial cell proliferation. The nonpathogenic Salmonella strain PhoP(c) activates the beta-catenin signaling pathway of human epithelia via a blockade of beta-catenin degradation. Normal beta-catenin ubiquitination necessary for constitutive beta-catenin degradation is abolished, allowing the accumulation and translocation of beta-catenin to the nucleus. Transcriptional activation mediated by the beta-catenin/T cell factor complex increases c-myc expression and enhances cell proliferation. We also show that the Salmonella effector protein AvrA is involved in modulating this beta-catenin activation. These data suggest that nonvirulent bacterial-epithelial interactions can influence beta-catenin signaling and cell growth control in a manner previously unsuspected.
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