Author | Ferrão, Patrícia M. | |
Author | Nisimura, Líndice M. | |
Author | Moreira, Otacilio C. | |
Author | Land, Marcelo G. | |
Author | Pereira, Mirian C. | |
Author | Lima, Leila de Mendonça | |
Author | Araujo-Jorge, Tania C. | |
Author | Waghabi, Mariana . | |
Author | Garzoni, Luciana R. | |
Access date | 2018-09-18T11:46:57Z | |
Available date | 2018-09-18T11:46:57Z | |
Document date | 2018 | |
Citation | FERRÃO, Patrícia M. et al. Inhibition of TGF-B pathway reverts extracellular matrix remodeling in T. cruzi-infected cardiac spheroids. Experimental Research, v. 362, p. 260-267, 2018. | pt_BR |
ISSN | 0014-4827 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/28842 | |
Language | eng | pt_BR |
Publisher | Elsevier | pt_BR |
Rights | restricted access | |
Subject in Portuguese | Trypanosoma Cruzi | pt_BR |
Subject in Portuguese | Matriz Extracelular | pt_BR |
Subject in Portuguese | Esferóides cardíacos | pt_BR |
Title | Inhibition of TGF-β pathway reverts extracellular matrix remodeling in T. cruzi-infected cardiac spheroids | pt_BR |
Type | Article | pt_BR |
DOI | 10.1016/j.yexcr.2017.11.026 | |
Abstract | Chagasic cardiomyopathy (CC) is the main manifestation of Chagas Disease (CD). CC is a progressive dysfunctional illness, in which transforming growth factor beta (TGF-β) plays a central role in fibrogenesis and hypertrophy. In the present study, we tested in a three-dimensional (3D) model of cardiac cells culture (named cardiac spheroids), capable of mimicking the aspects of fibrosis and hypertrophy observed in CC, the role of TGF-β pathway inhibition in restoring extracellular matrix (ECM) balance disrupted by T. cruzi infection. Treatment of T. cruzi-infected cardiac spheroids with SB 431542, a selective inhibitor of TGF-β type I receptor, resulted in a reduction in the size of spheroids, which was accompanied by a decrease in parasite load and in fibronectin expression. The inhibition of TGF-β pathway also promoted an increase in the activity of matrix metalloproteinase (MMP)-2 and a decrease in tissue inhibitor of matrix metalloproteinase (TIMP)-1 expression, which may be one of the mechanisms regulating extracellular matrix remodeling. Therefore, our study provides new insights into the molecular mechanisms by which inhibition of TGF-β signaling reverts fibrosis and hypertrophy generated by T. cruzi during CC and also highlights the use of cardiac spheroids as a valuable tool for the study of fibrogenesis and anti-fibrotic compounds. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | 3D Cell culture | pt_BR |
Subject | Cardiac spheroids | pt_BR |
Subject | Extracellular matrix | pt_BR |
Subject | TGF B | pt_BR |
Subject | SB 431542 | pt_BR |
Subject | T. cruzi | pt_BR |
DeCS | Fator de Crescimento Transformador beta | pt_BR |
Embargo date | 2030-01-01 | |