Gene Expression Profiling Specifies Chemokine, Mitochondrial and Lipid Metabolism Signatures in Leprosy

Detalhes bibliográficos
Autor(a) principal: Guerreiro, Luana Tatiana Albuquerque
Data de Publicação: 2013
Outros Autores: Ferreira, Anna Beatriz Robottom, Alves, Marcelo Ribeiro, Pinto, Thiago Gomes Toledo, Brito, Tiana Rosa, Rosa, Patrícia Sammarco, Sandoval, Felipe Galvan, Jardim, Márcia Rodrigues, Antunes, Sérgio Gomes, Shannon, Edward J., Sarno, Euzenir Nunes, Pessolani, Maria Cristina Vidal, Williams, Diana Lynn, Moraes, Milton Ozório
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/11741
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
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spelling Guerreiro, Luana Tatiana AlbuquerqueFerreira, Anna Beatriz RobottomAlves, Marcelo RibeiroPinto, Thiago Gomes ToledoBrito, Tiana RosaRosa, Patrícia SammarcoSandoval, Felipe GalvanJardim, Márcia RodriguesAntunes, Sérgio GomesShannon, Edward J.Sarno, Euzenir NunesPessolani, Maria Cristina VidalWilliams, Diana LynnMoraes, Milton Ozório2015-09-21T17:25:35Z2015-09-21T17:25:35Z2013GUERREIRO, Luana Tatiana Albuquerque. Gene Expression Profiling Specifies Chemokine, Mitochondrial and Lipid Metabolism Signatures in Leprosy. Plos One, v.8, n.6, 11p, 2013.https://www.arca.fiocruz.br/handle/icict/1174110.1371/journal.pone.0064748engPlos OneGene Expression Profiling Specifies Chemokine, Mitochondrial and Lipid Metabolism Signatures in Leprosyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Pesquisa em Farmacogenética. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Instituto Lauro de Souza Lima. Bauru, SP, Brasil.Louisiana State University. School of Veterinary Medicine. Laboratory Research Branch. Division of National Hansen’s Disease Programs. Bureau of Primary Health Care (BPHC). Health Resources and Services Administration (HRSA). Baton Rouge, Louisiana, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Louisiana State University. School of Veterinary Medicine. Laboratory Research Branch. Division of National Hansen’s Disease Programs. Bureau of Primary Health Care (BPHC). Health Resources and Services Administration (HRSA). Baton Rouge, Louisiana, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.Louisiana State University. School of Veterinary Medicine. Laboratory Research Branch. Division of National Hansen’s Disease Programs. Bureau of Primary Health Care (BPHC). Health Resources and Services Administration (HRSA). Baton Rouge, Louisiana, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Herein, we performed microarray experiments in Schwann cells infected with live M. leprae and identified novel differentially expressed genes (DEG) in M. leprae infected cells. Also, we selected candidate genes associated or implicated with leprosy in genetic studies and biological experiments. Forty-seven genes were selected for validation in two independent types of samples by multiplex qPCR. First, an in vitro model using THP-1 cells was infected with live Mycobacterium leprae and M. bovis bacillus Calmette-Gue´rin (BCG). In a second situation, mRNA obtained from nerve biopsies from patients with leprosy or other peripheral neuropathies was tested. We detected DEGs that discriminate M. bovis BCG from M. leprae infection. Specific signatures of susceptible responses after M. leprae infection when compared to BCG lead to repression of genes, including CCL2, CCL3, IL8 and SOD2. The same 47-gene set was screened in nerve biopsies, which corroborated the downregulation of CCL2 and CCL3 in leprosy, but also evidenced the down-regulation of genes involved in mitochondrial metabolism, and the up-regulation of genes involved in lipid metabolism and ubiquitination. Finally, a gene expression signature from DEG was identified in patients confirmed of having leprosy. A classification tree was able to ascertain 80% of the cases as leprosy or non-leprous peripheral neuropathy based on the expression of only LDLR and CCL4. A general immune and mitochondrial hypo-responsive state occurs in response to M. leprae infection. Also, the most important genes and pathways have been highlighted providing new tools for early diagnosis and treatment of leprosy.LeprosyLipid MetabolismChemokineMitochondrialGenesHanseníaseQuimiocinasMitocôndriasMetabolismo LipídicoGenesinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1914https://www.arca.fiocruz.br/bitstream/icict/11741/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINALluana_guerreiro_etal_IOC_2013.pdfapplication/pdf655014https://www.arca.fiocruz.br/bitstream/icict/11741/2/luana_guerreiro_etal_IOC_2013.pdf0489349e2bf296575474a3cd5b1a74dbMD52TEXTluana_guerreiro_etal_IOC_2013.pdf.txtluana_guerreiro_etal_IOC_2013.pdf.txtExtracted texttext/plain60376https://www.arca.fiocruz.br/bitstream/icict/11741/3/luana_guerreiro_etal_IOC_2013.pdf.txt6736a44224fabb377b9823634b35222dMD53icict/117412022-06-24 12:18:56.79oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352022-06-24T15:18:56Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Gene Expression Profiling Specifies Chemokine, Mitochondrial and Lipid Metabolism Signatures in Leprosy
title Gene Expression Profiling Specifies Chemokine, Mitochondrial and Lipid Metabolism Signatures in Leprosy
spellingShingle Gene Expression Profiling Specifies Chemokine, Mitochondrial and Lipid Metabolism Signatures in Leprosy
Guerreiro, Luana Tatiana Albuquerque
Leprosy
Lipid Metabolism
Chemokine
Mitochondrial
Genes
Hanseníase
Quimiocinas
Mitocôndrias
Metabolismo Lipídico
Genes
title_short Gene Expression Profiling Specifies Chemokine, Mitochondrial and Lipid Metabolism Signatures in Leprosy
title_full Gene Expression Profiling Specifies Chemokine, Mitochondrial and Lipid Metabolism Signatures in Leprosy
title_fullStr Gene Expression Profiling Specifies Chemokine, Mitochondrial and Lipid Metabolism Signatures in Leprosy
title_full_unstemmed Gene Expression Profiling Specifies Chemokine, Mitochondrial and Lipid Metabolism Signatures in Leprosy
title_sort Gene Expression Profiling Specifies Chemokine, Mitochondrial and Lipid Metabolism Signatures in Leprosy
author Guerreiro, Luana Tatiana Albuquerque
author_facet Guerreiro, Luana Tatiana Albuquerque
Ferreira, Anna Beatriz Robottom
Alves, Marcelo Ribeiro
Pinto, Thiago Gomes Toledo
Brito, Tiana Rosa
Rosa, Patrícia Sammarco
Sandoval, Felipe Galvan
Jardim, Márcia Rodrigues
Antunes, Sérgio Gomes
Shannon, Edward J.
Sarno, Euzenir Nunes
Pessolani, Maria Cristina Vidal
Williams, Diana Lynn
Moraes, Milton Ozório
author_role author
author2 Ferreira, Anna Beatriz Robottom
Alves, Marcelo Ribeiro
Pinto, Thiago Gomes Toledo
Brito, Tiana Rosa
Rosa, Patrícia Sammarco
Sandoval, Felipe Galvan
Jardim, Márcia Rodrigues
Antunes, Sérgio Gomes
Shannon, Edward J.
Sarno, Euzenir Nunes
Pessolani, Maria Cristina Vidal
Williams, Diana Lynn
Moraes, Milton Ozório
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Guerreiro, Luana Tatiana Albuquerque
Ferreira, Anna Beatriz Robottom
Alves, Marcelo Ribeiro
Pinto, Thiago Gomes Toledo
Brito, Tiana Rosa
Rosa, Patrícia Sammarco
Sandoval, Felipe Galvan
Jardim, Márcia Rodrigues
Antunes, Sérgio Gomes
Shannon, Edward J.
Sarno, Euzenir Nunes
Pessolani, Maria Cristina Vidal
Williams, Diana Lynn
Moraes, Milton Ozório
dc.subject.en.pt_BR.fl_str_mv Leprosy
Lipid Metabolism
Chemokine
Mitochondrial
Genes
topic Leprosy
Lipid Metabolism
Chemokine
Mitochondrial
Genes
Hanseníase
Quimiocinas
Mitocôndrias
Metabolismo Lipídico
Genes
dc.subject.decs.pt_BR.fl_str_mv Hanseníase
Quimiocinas
Mitocôndrias
Metabolismo Lipídico
Genes
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
publishDate 2013
dc.date.issued.fl_str_mv 2013
dc.date.accessioned.fl_str_mv 2015-09-21T17:25:35Z
dc.date.available.fl_str_mv 2015-09-21T17:25:35Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv GUERREIRO, Luana Tatiana Albuquerque. Gene Expression Profiling Specifies Chemokine, Mitochondrial and Lipid Metabolism Signatures in Leprosy. Plos One, v.8, n.6, 11p, 2013.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/11741
dc.identifier.doi.pt_BR.fl_str_mv 10.1371/journal.pone.0064748
identifier_str_mv GUERREIRO, Luana Tatiana Albuquerque. Gene Expression Profiling Specifies Chemokine, Mitochondrial and Lipid Metabolism Signatures in Leprosy. Plos One, v.8, n.6, 11p, 2013.
10.1371/journal.pone.0064748
url https://www.arca.fiocruz.br/handle/icict/11741
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Plos One
publisher.none.fl_str_mv Plos One
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
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