|
KMID : 0613820180280091016
|
|
Journal of Life Science
2018 Volume.28 No. 9 p.1016 ~ p.1021
|
|
|
Clostridium difficile Toxin A Inhibits Wnt Signaling Pathway in Gut Epithelial Cells
|
|
Yoon I-Na
Kim Ho
|
|
|
Abstract
|
|
|
|
Clostridium difficile toxin A causes pseudomembranous colitis. The pathogenesis of toxin A-induced colonic inflammation includes toxin A-dependent epithelial cell apoptosis, resulting in the loss of barrier function provided by epithelial cells against luminal pathogens. Toxin A-dependent epithelial cell apoptosis has been linked to toxin A-induced production of reaction oxygen species and subsequent p38MAPK activation; p21CIP1/WAF1 upregulation-dependent cell cycle arrest; cytoskeletal disaggregation; and/or the induction of Fas ligand on epithelial cells. However, the molecular mechanisms underlying toxin A-induced apoptosis remain poorly understood. This study tested whether toxin A could block the Wnt signaling pathway, which is involved in gut epithelial cell proliferation, differentiation and antiapoptotic progression. Toxin A treatment of nontransformed human colonocytes (NCM460) rapidly reduced β-catenin protein, an essential component of the Wnt signaling pathway. Exposure of mouse ileum to toxin A also significantly reduced β-catenin protein levels. MG132 inhibition of proteasome-dependent protein degradation resulted in the recovery of toxin A-mediated reduction of β-catenin, indicating that toxin A may activate intracellular processes, such as GSK3β, to promote degradation of β-catenin. Immunoblot analysis showed that toxin A increased active phosphorylation of GSK3β. Because the Wnt signaling pathway is essential for gut epithelial cell proliferation and anti-apoptotic processes, our results suggest that toxin A-mediated inhibition of the Wnt signaling pathway may be required for maximal toxin A-induced apoptosis of gut epithelial cells.
|
|
|
KEYWORD
|
|
|
β-catenin, Clostridium difficile toxin A, colitis, epithelial cells, nt signaling
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|