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Title in Portuguese: Clostridium difficile toxin A attenuates Wnt/B-Catenin signaling in intestinal epithelial cells
Author: Lima, Bruno Bezerra
Fonseca, Bárbara Faria
Amado, Nathália da Graça
Lima, Débora Moreira
Ribeiro, Ronaldo Albuquerque
Abreu, José Garcia
Brito, Gerly Anne de Castro
Keywords: Clostridium difficile
Células Epiteliais
Issue Date: Jul-2014
Publisher: Infection and Immunity
Citation: 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.
Abstract in Portuguese: 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.
metadata.dc.type: Artigo de Periódico
ISSN: 1098-5522 Online
Appears in Collections:DFIFA - Artigos publicados em revista científica

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