Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/28842
Title: Inhibition of TGF-β pathway reverts extracellular matrix remodeling in T. cruzi-infected cardiac spheroids
Authors: Ferrão, Patrícia M.
Nisimura, Líndice M.
Moreira, Otacílio C.
Land, Marcelo G.
Pereira, Mirian C.
Lima, Leila de Mendonça
Araujo-Jorge, Tania C.
Waghabi, Mariana .
Garzoni, Luciana R.
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.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.
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.
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.
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.
Keywords: 3D Cell culture
Cardiac spheroids
Extracellular matrix
TGF B
SB 431542
T. cruzi
keywords: Trypanosoma Cruzi
Matriz Extracelular
Esferóides cardíacos
DeCS: Fator de Crescimento Transformador beta
Issue Date: 2018
Publisher: Elsevier
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.
DOI: 10.1016/j.yexcr.2017.11.026
ISSN: 0014-4827
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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