Transforming growth factor β1/SMAD signaling pathway activation protects the intestinal epithelium from Clostridium difficile toxin A-induced damage
| Autor: | Tinoco-Veras, Christianne Maria, Santos, Ana Angélica Q. A., Stipursky, Joice, Meloni, Marcelo, Araujo, Ana Paula Bérgamo, Foschetti, Danielle Abreu, López-Ureña, Diana, Quesada-Gómez, Carlos, Leitão, Renata Ferreira de Carvalho, Gomes, Flávia Carvalho Alcantara, Brito, Gerly Anne de Castro |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Repositório Institucional da Universidade Federal do Ceará (UFC) Universidade Federal do Ceará (UFC) instacron:UFC |
| Popis: | Clostridium difficile , the main cause of diarrhea in hospitalized patients, produces toxins A (TcdA) and B (TcdB), which affect intestinal epithelial cell survival, proliferation, and migration and induce an intense inflammatory response. Trans- forming growth factor (TGF- ) is a pleiotropic cytokine affecting enterocyte and immune/inflammatory responses. However, it has been shown that exposure of in- testinal epithelium to a low concentration of TcdA induces the release of TGF- 1, which has a protective effect on epithelial resistance and a TcdA/TGF- signaling pathway interaction. The activation of this pathway in vivo has not been elucidated. The aim of this study was to investigate the role of the TGF- 1 pathway in TcdA- induced damage in a rat intestinal epithelial cell line (IEC-6) and in a mouse model of an ileal loop. TcdA increased the expression of TGF- 1 and its receptor, T RII, in vitro and in vivo . TcdA induced nuclear translocation of the transcription factors SMAD2/3, a hallmark of TGF- 1 pathway activation, both in IEC cells and in mouse ileal tissue. The addition of recombinant TGF- 1 (rTGF- ) prevented TcdA-induced apoptosis/necrosis and restored proliferation and repair activity in IEC-6 cells in the presence of TcdA. Together, these data show that TcdA induces TGF- 1 signaling pathway activation and suggest that this pathway might play a protective role against the effect of C. difficile -toxin. |
| Databáze: | OpenAIRE |
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