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Tipo:	Artigo de Periódico
Título:	Clostridium difficile toxin A attenuates Wnt/B-Catenin signaling in intestinal epithelial cells
Autor(es):	Lima, Bruno Bezerra Fonseca, Bárbara Faria Amado, Nathália da Graça Lima, Débora Moreira Ribeiro, Ronaldo Albuquerque Abreu, José Garcia Brito, Gerly Anne de Castro
Palavras-chave:	Clostridium difficile;Células Epiteliais
Data do documento:	Jul-2014
Instituição/Editor/Publicador:	Infection and Immunity
Citação:	LIMA, B. B. et al. Clostridium difficile Toxin A attenuates Wnt/B-Catenin signaling in intestinal epithelial cells. Infection and Immunity, Washington, v. 82, n. 7, p. 2680–2687, jul. 2014.
Resumo:	Clostridium difficile toxins A and B (TcdA and TcdB) are homologous glycosyltransferases that inhibit a group of small GTPases within host cells, but several mechanisms underlying their pathogenic activity remain unclear. In this study, we evaluated the effects of TcdA on the Wnt/ -catenin pathway, the major driving force behind the proliferation of epithelial cells in colonic crypts. IEC-6 and RKO cells stimulated with Wnt3a-conditioned medium were incubated with 10, 50, and 100 ng/ml of TcdA for 24 h, resulting in a dose-dependent inhibition of the Wnt signaling, as demonstrated by a T-cell factor (TCF) reporter assay. This was further confirmed by immunofluorescence staining for nuclear localization of -catenin and Western blotting for -catenin and c-Myc (encoded by a Wnt target gene). Moreover, our Western blot analysis showed a decrease in the -catenin protein levels, which was reversed by z-VAD-fmk, a pan-caspase inhibitor. Nonetheless, TcdA was still able to inhibit the Wnt/ -catenin pathway even in the presence of z-VAD-fmk, lithium chloride (a GSK3 inhibitor), or constitutively active -catenin, as determined by a TCF reporter assay. Furthermore, preincubation of RKO cells with TcdA for 12 h also attenuated Wnt3a-mediated activation of Wnt signaling, suggesting that inactivation of Rho GTPases plays a significant role in that inhibition. Taken together, these findings suggest that attenuation of the Wnt signaling by TcdA is important for TcdA antiproliferative effects.
URI:	http://www.repositorio.ufc.br/handle/riufc/12280
ISSN:	1098-5522 Online
Aparece nas coleções:	DFIFA - Artigos publicados em revista científica

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