Emerging Role of HMGB1 in the Pathogenesis of Schistosomiasis Liver Fibrosis
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2018 |
| Outros Autores: | , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/33553 |
Resumo: | Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brazil |
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Vicentino, Amanda Roberta RevoredoCarneiro, Vitor CoutinhoAllonso, DiegoGuilherme, Rafael de FreitasBenjamim, Claudia FariasSantos, Hilton Antonio Mata dosXavier, FabíolaPyrrho, Alexandre dos SantosGomes, Juliana de Assis SilvaFonseca, Matheus de CastroOliveira, Rodrigo Corrêa dePereira, Thiago A.Ladislau, LeandroLambertucci, José RobertoFantappié, Marcelo Rosado2019-06-18T16:45:54Z2019-06-18T16:45:54Z2018VICENTINO, Amanda Roberta Revoredo et al. Emerging Role of HMGB1 in the Pathogenesis of Schistosomiasis Liver Fibrosis. Front Immunol., 9, 1979, 2018.1664-3224https://www.arca.fiocruz.br/handle/icict/3355310.3389/fimmu.2018.01979. eCollection 2018engFrontiers Research FoundationEsquistossomoseHMGB1schistosomiasisHMGB1granulomaliver fibrosisdrugs therapyEmerging Role of HMGB1 in the Pathogenesis of Schistosomiasis Liver Fibrosisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, BrazilUniversidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, BrazilUniversidade Federal do Rio de Janeiro. Faculdade de Farmácia. Departamento de Biotecnologia Farmacêutica. Rio de Janeiro, RJ, BrazilUniversidade Federal do Rio de Janeiro. Departamento de Farmacologia Básica e Clínica. Rio de Janeiro, RJ, BrazilUniversidade Federal do Rio de Janeiro. Departamento de Farmacologia Básica e Clínica. Rio de Janeiro, RJ, BrazilUniversidade Federal do Rio de Janeiro. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Rio de Janeiro, RJ, BrazilUniversidade Federal do Rio de Janeiro. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Rio de Janeiro, RJ, BrazilUniversidade Federal do Rio de Janeiro. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Rio de Janeiro, RJ, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Belo Horizonte, MG, BrazilCentro de Pesquisa em Energia e Materiais. Laboratório Nacional de Biociências. Campinas, SP, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrazilInstitute for Stem Cell Biology and Regenerative Medicine. Stanford University School of Medicine. Stanford, CA, United StatesUniversidade Federal do Rio de Janeiro. Departamento de Farmacologia Básica e Clínica. Rio de Janeiro, RJ, BrazilUniversidade Federal de Minas Gerais. Faculdade de Medicina. Belo Horizonte, MG, BrazilUniversidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, BrazilIn chronic schistosomiasis, liver fibrosis is linked to portal hypertension, which is a condition associated with high mortality and morbidity. High mobility group box 1 (HMGB1) was originally described as a nuclear protein that functions as a structural co-factor in transcriptional regulation. However, HMGB1 can also be secreted into the extracellular milieu under appropriate signal stimulation. Extracellular HMGB1 acts as a multifunctional cytokine that contributes to infection, injury, inflammation, and immune responses by binding to specific cell-surface receptors. HMGB1 is involved in fibrotic diseases. From a clinical perspective, HMGB1 inhibition may represent a promising therapeutic approach for treating tissue fibrosis. In this study, we demonstrate elevated levels of HMGB1 in the sera in experimental mice or in patients with schistosomiasis. Using immunohistochemistry, we demonstrated that HMGB1 trafficking in the hepatocytes of mice suffering from acute schistosomiasis was inhibited by Glycyrrhizin, a well-known HMGB1 direct inhibitor, as well as by DIC, a novel and potential anti-HMGB1 compound. HMGB1 inhibition led to significant downregulation of IL-6, IL4, IL-5, IL-13, IL-17A, which are involved in the exacerbation of the immune response and liver fibrogenesis. Importantly, infected mice that were treated with DIC or GZR to inhibit HMGB1 pro-inflammatory activity showed a significant increase in survival and a reduction of over 50% in the area of liver fibrosis. Taken together, our findings indicate that HMGB1 is a key mediator of schistosomotic granuloma formation and liver fibrosis and may represent an outstanding target for the treatment of schistosomiasis.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83082https://www.arca.fiocruz.br/bitstream/icict/33553/1/license.txt9193a7c197bc67acd023525e72a03240MD51ORIGINALEmerging Role of HMGB1.pdfEmerging Role of HMGB1.pdfapplication/pdf5241117https://www.arca.fiocruz.br/bitstream/icict/33553/2/Emerging%20Role%20of%20HMGB1.pdfae2a9e6609d1dd84fc7ea749c4e441c8MD52TEXTEmerging Role of HMGB1.pdf.txtEmerging Role of HMGB1.pdf.txtExtracted texttext/plain73508https://www.arca.fiocruz.br/bitstream/icict/33553/3/Emerging%20Role%20of%20HMGB1.pdf.txt1407fc0e5938d65614f04e1b5125a25aMD53icict/335532019-06-19 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| dc.title.pt_BR.fl_str_mv |
Emerging Role of HMGB1 in the Pathogenesis of Schistosomiasis Liver Fibrosis |
| title |
Emerging Role of HMGB1 in the Pathogenesis of Schistosomiasis Liver Fibrosis |
| spellingShingle |
Emerging Role of HMGB1 in the Pathogenesis of Schistosomiasis Liver Fibrosis Vicentino, Amanda Roberta Revoredo Esquistossomose HMGB1 schistosomiasis HMGB1 granuloma liver fibrosis drugs therapy |
| title_short |
Emerging Role of HMGB1 in the Pathogenesis of Schistosomiasis Liver Fibrosis |
| title_full |
Emerging Role of HMGB1 in the Pathogenesis of Schistosomiasis Liver Fibrosis |
| title_fullStr |
Emerging Role of HMGB1 in the Pathogenesis of Schistosomiasis Liver Fibrosis |
| title_full_unstemmed |
Emerging Role of HMGB1 in the Pathogenesis of Schistosomiasis Liver Fibrosis |
| title_sort |
Emerging Role of HMGB1 in the Pathogenesis of Schistosomiasis Liver Fibrosis |
| author |
Vicentino, Amanda Roberta Revoredo |
| author_facet |
Vicentino, Amanda Roberta Revoredo Carneiro, Vitor Coutinho Allonso, Diego Guilherme, Rafael de Freitas Benjamim, Claudia Farias Santos, Hilton Antonio Mata dos Xavier, Fabíola Pyrrho, Alexandre dos Santos Gomes, Juliana de Assis Silva Fonseca, Matheus de Castro Oliveira, Rodrigo Corrêa de Pereira, Thiago A. Ladislau, Leandro Lambertucci, José Roberto Fantappié, Marcelo Rosado |
| author_role |
author |
| author2 |
Carneiro, Vitor Coutinho Allonso, Diego Guilherme, Rafael de Freitas Benjamim, Claudia Farias Santos, Hilton Antonio Mata dos Xavier, Fabíola Pyrrho, Alexandre dos Santos Gomes, Juliana de Assis Silva Fonseca, Matheus de Castro Oliveira, Rodrigo Corrêa de Pereira, Thiago A. Ladislau, Leandro Lambertucci, José Roberto Fantappié, Marcelo Rosado |
| author2_role |
author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Vicentino, Amanda Roberta Revoredo Carneiro, Vitor Coutinho Allonso, Diego Guilherme, Rafael de Freitas Benjamim, Claudia Farias Santos, Hilton Antonio Mata dos Xavier, Fabíola Pyrrho, Alexandre dos Santos Gomes, Juliana de Assis Silva Fonseca, Matheus de Castro Oliveira, Rodrigo Corrêa de Pereira, Thiago A. Ladislau, Leandro Lambertucci, José Roberto Fantappié, Marcelo Rosado |
| dc.subject.other.pt_BR.fl_str_mv |
Esquistossomose HMGB1 |
| topic |
Esquistossomose HMGB1 schistosomiasis HMGB1 granuloma liver fibrosis drugs therapy |
| dc.subject.en.pt_BR.fl_str_mv |
schistosomiasis HMGB1 granuloma liver fibrosis drugs therapy |
| description |
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brazil |
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2018 |
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2018 |
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2019-06-18T16:45:54Z |
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2019-06-18T16:45:54Z |
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VICENTINO, Amanda Roberta Revoredo et al. Emerging Role of HMGB1 in the Pathogenesis of Schistosomiasis Liver Fibrosis. Front Immunol., 9, 1979, 2018. |
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https://www.arca.fiocruz.br/handle/icict/33553 |
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1664-3224 |
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10.3389/fimmu.2018.01979. eCollection 2018 |
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VICENTINO, Amanda Roberta Revoredo et al. Emerging Role of HMGB1 in the Pathogenesis of Schistosomiasis Liver Fibrosis. Front Immunol., 9, 1979, 2018. 1664-3224 10.3389/fimmu.2018.01979. eCollection 2018 |
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