The Search for Biomarkers and Treatments in Chagas Disease: Insights From TGF-Beta Studies and Immunogenetics

Detalhes bibliográficos
Autor(a) principal: Ferreira, Roberto Rodrigues
Data de Publicação: 2022
Outros Autores: Waghabi, Mariana Caldas, Bailly, Sabine, Feige, Jean-Jacques, Hasslocher-Moreno, Alejandro Marcel, Saraiva, Roberto M., Araujo-Jorge, Tania C.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/52658
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Educação e Bioprodutos. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil.
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spelling Ferreira, Roberto RodriguesWaghabi, Mariana CaldasBailly, SabineFeige, Jean-JacquesHasslocher-Moreno, Alejandro MarcelSaraiva, Roberto M.Araujo-Jorge, Tania C.2022-05-13T13:46:08Z2022-05-13T13:46:08Z2022FERREIRA, Roberto Rodrigues et al. The Search for Biomarkers and Treatments in Chagas Disease: Insights From TGF-Beta Studies and Immunogenetics. Frontiers in Cellular and Infection Microbiology, v. 11, p. 1-9, 2022.2235-2988https://www.arca.fiocruz.br/handle/icict/5265810.3389/fcimb.2021.767576engFrontiers MediaThe Search for Biomarkers and Treatments in Chagas Disease: Insights From TGF-Beta Studies and Immunogeneticsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Educação 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 Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil.Commissariat à l'Energie Atomique. Inserm. Université Grenoble Alpes. Laboratory Biology of Cancer and Infection. Grenoble, France.Commissariat à l'Energie Atomique. Inserm. Université Grenoble Alpes. Laboratory Biology of Cancer and Infection. Grenoble, France.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica da Doença de Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica da Doença de Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Educação e Bioprodutos. Rio de Janeiro, RJ, Brasil.The anti-inflammatory cytokine transforming growth factor beta (TGF-β) plays an important role in Chagas disease (CD), a potentially life-threatening illness caused by Trypanosoma cruzi. In this review we revisited clinical studies in CD patients combined with in vitro and in vivo experiments, presenting three main sections: an overview of epidemiological, economic, and clinical aspects of CD and the need for new biomarkers and treatment; a brief panorama of TGF-β roles and its intracellular signaling pathways, and an update of what is known about TGF-β and Chagas disease. In in vitro assays, TGF-β increases during T. cruzi infection and modulates heart cells invasion by the parasite fostering its intracellular parasite cycle. TGF-β modulates host immune response and inflammation, increases heart fibrosis, stimulates remodeling, and slows heart conduction via gap junction modulation. TGF-β signaling inhibitors reverts these effects opening a promising therapeutic approach in pre-clinical studies. CD patients with higher TGF-β1 serum level show a worse clinical outcome, implicating a predictive value of serum TGF-β as a surrogate biomarker of clinical relevance. Moreover, pre-clinical studies in chronic T. cruzi infected mice proved that inhibition of TGF-β pathway improved several cardiac electric parameters, reversed the loss of connexin-43 enriched intercellular plaques, reduced fibrosis of the cardiac tissue, restored GATA-6 and Tbox-5 transcription, supporting cardiac recovery. Finally, TGF-β polymorphisms indicate that CD immunogenetics is at the base of this phenomenon. We searched in a Brazilian population five single-nucleotide polymorphisms (-800 G>A rs1800468, -509 C>T rs1800469, +10 T>C rs1800470, +25 G>C rs1800471, and +263 C>T rs1800472), showing that CD patients frequently express the TGF-β1 gene genotypes CT and TT at position -509, as compared to noninfected persons; similar results were observed with genotypes TC and CC at codon +10 of the TGF-β1 gene, leading to the conclusion that 509 C>T and +10 T>C TGF-β1 polymorphisms are associated with Chagas disease susceptibility. Studies in genetically different populations susceptible to CD will help to gather new insights and encourage the use of TGF-β as a CD biomarker.Chagas diseaseTGF-betaBiomarkerFibrosisPolymorphisminfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83099https://www.arca.fiocruz.br/bitstream/icict/52658/1/license.txt586c046dcfeef936e32f0323bb9a47c0MD51ORIGINALThe Search_Alejandro_Moreno_etal_INI_2022.pdfThe Search_Alejandro_Moreno_etal_INI_2022.pdfapplication/pdf24861980https://www.arca.fiocruz.br/bitstream/icict/52658/2/The%20Search_Alejandro_Moreno_etal_INI_2022.pdf560bb4045c38ea8b20cc4428803c326eMD52icict/526582023-03-08 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dc.title.pt_BR.fl_str_mv The Search for Biomarkers and Treatments in Chagas Disease: Insights From TGF-Beta Studies and Immunogenetics
title The Search for Biomarkers and Treatments in Chagas Disease: Insights From TGF-Beta Studies and Immunogenetics
spellingShingle The Search for Biomarkers and Treatments in Chagas Disease: Insights From TGF-Beta Studies and Immunogenetics
Ferreira, Roberto Rodrigues
Chagas disease
TGF-beta
Biomarker
Fibrosis
Polymorphism
title_short The Search for Biomarkers and Treatments in Chagas Disease: Insights From TGF-Beta Studies and Immunogenetics
title_full The Search for Biomarkers and Treatments in Chagas Disease: Insights From TGF-Beta Studies and Immunogenetics
title_fullStr The Search for Biomarkers and Treatments in Chagas Disease: Insights From TGF-Beta Studies and Immunogenetics
title_full_unstemmed The Search for Biomarkers and Treatments in Chagas Disease: Insights From TGF-Beta Studies and Immunogenetics
title_sort The Search for Biomarkers and Treatments in Chagas Disease: Insights From TGF-Beta Studies and Immunogenetics
author Ferreira, Roberto Rodrigues
author_facet Ferreira, Roberto Rodrigues
Waghabi, Mariana Caldas
Bailly, Sabine
Feige, Jean-Jacques
Hasslocher-Moreno, Alejandro Marcel
Saraiva, Roberto M.
Araujo-Jorge, Tania C.
author_role author
author2 Waghabi, Mariana Caldas
Bailly, Sabine
Feige, Jean-Jacques
Hasslocher-Moreno, Alejandro Marcel
Saraiva, Roberto M.
Araujo-Jorge, Tania C.
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Ferreira, Roberto Rodrigues
Waghabi, Mariana Caldas
Bailly, Sabine
Feige, Jean-Jacques
Hasslocher-Moreno, Alejandro Marcel
Saraiva, Roberto M.
Araujo-Jorge, Tania C.
dc.subject.en.pt_BR.fl_str_mv Chagas disease
TGF-beta
Biomarker
Fibrosis
Polymorphism
topic Chagas disease
TGF-beta
Biomarker
Fibrosis
Polymorphism
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Educação e Bioprodutos. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil.
publishDate 2022
dc.date.accessioned.fl_str_mv 2022-05-13T13:46:08Z
dc.date.available.fl_str_mv 2022-05-13T13:46:08Z
dc.date.issued.fl_str_mv 2022
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv FERREIRA, Roberto Rodrigues et al. The Search for Biomarkers and Treatments in Chagas Disease: Insights From TGF-Beta Studies and Immunogenetics. Frontiers in Cellular and Infection Microbiology, v. 11, p. 1-9, 2022.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/52658
dc.identifier.issn.pt_BR.fl_str_mv 2235-2988
dc.identifier.doi.none.fl_str_mv 10.3389/fcimb.2021.767576
identifier_str_mv FERREIRA, Roberto Rodrigues et al. The Search for Biomarkers and Treatments in Chagas Disease: Insights From TGF-Beta Studies and Immunogenetics. Frontiers in Cellular and Infection Microbiology, v. 11, p. 1-9, 2022.
2235-2988
10.3389/fcimb.2021.767576
url https://www.arca.fiocruz.br/handle/icict/52658
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/52658/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/52658/2/The%20Search_Alejandro_Moreno_etal_INI_2022.pdf
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
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