4.3 Article

Proteins involved on TGF-β pathway are up-regulated during the acute phase of experimental Chagas disease

期刊

IMMUNOBIOLOGY
卷 221, 期 5, 页码 587-594

出版社

ELSEVIER GMBH
DOI: 10.1016/j.imbio.2016.01.009

关键词

Trypanosoma cruzi; TGF-beta; Infection; Chagas disease; Fibrosis

资金

  1. INSERM-FIOCRUZ collaborative program
  2. Fundacao Oswaldo Cruz (FIOCRUZ)
  3. Programa Estrategico de Apoio a Pesquisa em Saude (PAPES)
  4. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)

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Studies developed by our group in the last years have shown the involvement of TGF-beta in acute and chronic Chagas heart disease, with elevated plasma levels and activated TGF-beta cell signaling pathway as remarkable features of patients in the advanced stages of this disease, when high levels of cardiac fibrosis is present. Imbalance in synthesis and degradation of extracellular matrix components is the basis of pathological fibrosis and TGF-beta is considered as one of the key regulators of this process. In the present study, we investigated the activity of the TGF-beta signaling pathway, including receptors and signaling proteins activation in the heart of animals experimentally infected with Trypanosoma cruzi during the period that mimics the acute phase of Chagas disease. We observed that T. cruzi infected animals presented increased expression of TGF-beta receptors. Overexpression of receptors was followed by an increased phosphorylation of Smad2/3, p38 and ERIC. Furthermore, we correlated these activities with cellular factors involved in the fibrotic process induced by TGF-beta. We observed that the expression of collagen I, fibronectin and CTGF were increased in the heart of infected animals on day 15 post-infection. Correlated with the increased TGF-beta activity in the heart, we found that serum levels of total TGF-beta were significantly higher during acute infection. Taken together, our data suggest that the commitment of the heart associates with increased activity of TGF-beta pathway and expression of its main components. Our results, confirm the importance of this cytokine in the development and maintenance of cardiac damage caused by T. cruzi infection. (C) 2016 Elsevier GmbH. All rights reserved.

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