title: Proteins involved on TGF-β pathway are up-regulated during the acute phase of experimental Chagas disease.
abstract: Studies developed by our group in the last years have shown the involvement of TGF-β in acute and chronic Chagas heart disease, with elevated plasma levels and activated TGF-β 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-β is considered as one of the key regulators of this process. In the present study, we investigated the activity of the TGF-β 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-β receptors. Overexpression of receptors was followed by an increased phosphorylation of Smad2/3, p38 and ERK. Furthermore, we correlated these activities with cellular factors involved in the fibrotic process induced by TGF-β. 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-β activity in the heart, we found that serum levels of total TGF-β were significantly higher during acute infection. Taken together, our data suggest that the commitment of the heart associates with increased activity of TGF-β 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.
authors: Laboratório de Genômica Funcional e Bioinformática-Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro RJ, Brazil.
authors: Roberto Rodrigues
authors: RR
authors: Ferreira
authors: Laboratório de Inovações em Terapias, Ensino e Bioprodutos-Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro RJ, Brazil.
authors: Elen Mello
authors: EM
authors: de Souza
authors: Laboratório de Genômica Funcional e Bioinformática-Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro RJ, Brazil.
authors: Fabiane Loiola
authors: FL
authors: de Oliveira
authors: Laboratório de Genômica Funcional e Bioinformática-Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro RJ, Brazil.
authors: Patrícia Mello
authors: PM
authors: Ferrão
authors: Laboratório de Genômica Funcional e Bioinformática-Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro RJ, Brazil.
authors: Leonardo Henrique Ferreira
authors: LH
authors: Gomes
authors: Laboratório de Genômica Funcional e Bioinformática-Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro RJ, Brazil.
authors: Leila
authors: L
authors: Mendonça-Lima
authors: Laboratório de Inovações em Terapias, Ensino e Bioprodutos-Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro RJ, Brazil.
authors: Marcelo
authors: M
authors: Meuser-Batista
authors: INSERM, U1036, Grenoble F-38000, France; University Grenoble-Alpes, Grenoble F-38000, France; CEA, DSV, iRTSV, Laboratory of Biology of Cancer and Infection, Grenoble F-38000, France.
authors: Sabine
authors: S
authors: Bailly
authors: INSERM, U1036, Grenoble F-38000, France; University Grenoble-Alpes, Grenoble F-38000, France; CEA, DSV, iRTSV, Laboratory of Biology of Cancer and Infection, Grenoble F-38000, France.
authors: Jean Jacques
authors: JJ
authors: Feige
authors: Laboratório de Inovações em Terapias, Ensino e Bioprodutos-Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro RJ, Brazil.
authors: Tania Cremonini
authors: TC
authors: de Araujo-Jorge
authors: Laboratório de Genômica Funcional e Bioinformática-Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro RJ, Brazil. Electronic address: mariana@ioc.fiocruz.br.
authors: Mariana Caldas
authors: MC
authors: Waghabi
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000378:metabolism* / Q000401:mortality / Q000469:parasitology / Q000473:pathology; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000097:blood / Q000378:metabolism*; D014349:Trypanosoma cruzi; D015854:Up-Regulation
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta
keywords: Chagas disease; Fibrosis; Infection; TGF-β; Trypanosoma cruzi