Genetic disruption of NRF2 promotes the development of necroinflammation and liver fibrosis in a mouse model of HFE-hereditary hemochromatosis
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.16/2180 |
Resumo: | In hereditary hemochromatosis, iron deposition in the liver parenchyma may lead to fibrosis, cirrhosis and hepatocellular carcinoma. Most cases are ascribed to a common mutation in the HFE gene, but the extent of clinical expression is greatly influenced by the combined action of yet unidentified genetic and/or environmental modifying factors. In mice, transcription factor NRF2 is a critical determinant of hepatocyte viability during exposure to acute dietary iron overload. We evaluated if the genetic disruption of Nrf2 would prompt the development of liver damage in Hfe(-/-) mice (an established model of human HFE-hemochromatosis). |
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Genetic disruption of NRF2 promotes the development of necroinflammation and liver fibrosis in a mouse model of HFE-hereditary hemochromatosisHepatocyteIronMacrophageOxidative stressSideronecrosisIn hereditary hemochromatosis, iron deposition in the liver parenchyma may lead to fibrosis, cirrhosis and hepatocellular carcinoma. Most cases are ascribed to a common mutation in the HFE gene, but the extent of clinical expression is greatly influenced by the combined action of yet unidentified genetic and/or environmental modifying factors. In mice, transcription factor NRF2 is a critical determinant of hepatocyte viability during exposure to acute dietary iron overload. We evaluated if the genetic disruption of Nrf2 would prompt the development of liver damage in Hfe(-/-) mice (an established model of human HFE-hemochromatosis).This work was supported by National funds through Fundação para a Ciência e a Tecnologia/Ministério da Educação e Ciência (PTDC/SAU-FCF/101177/2008, PTDC/BIM-MET/0739/2012 and SFRH/BPD/108207/2015), by FEDER funds through the COMPETE – Operational Competitiveness Programme (FCOMP-01-0124-FEDER-011062 and FCOMP-01-0124-FEDER-028447) and Project Norte-01-0145-FEDER-000012, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and by Reitoria da Universidade do Porto/Santander through PP-IJUP2011-122.ElsevierRepositório Científico do Centro Hospitalar Universitário de Santo AntónioDuarte, T.Caldas, C.Santos, A.Silva-Gomes, S.Santos-Gonçalves, A.Martins, M.Porto, G.Lopes, J.2017-09-04T17:21:55Z2017-042017-04-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.16/2180engRedox Biol. 2017 Apr;11:157-1692213-231710.1016/j.redox.2016.11.013info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-10-20T10:59:27Zoai:repositorio.chporto.pt:10400.16/2180Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:38:25.177292Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Genetic disruption of NRF2 promotes the development of necroinflammation and liver fibrosis in a mouse model of HFE-hereditary hemochromatosis |
title |
Genetic disruption of NRF2 promotes the development of necroinflammation and liver fibrosis in a mouse model of HFE-hereditary hemochromatosis |
spellingShingle |
Genetic disruption of NRF2 promotes the development of necroinflammation and liver fibrosis in a mouse model of HFE-hereditary hemochromatosis Duarte, T. Hepatocyte Iron Macrophage Oxidative stress Sideronecrosis |
title_short |
Genetic disruption of NRF2 promotes the development of necroinflammation and liver fibrosis in a mouse model of HFE-hereditary hemochromatosis |
title_full |
Genetic disruption of NRF2 promotes the development of necroinflammation and liver fibrosis in a mouse model of HFE-hereditary hemochromatosis |
title_fullStr |
Genetic disruption of NRF2 promotes the development of necroinflammation and liver fibrosis in a mouse model of HFE-hereditary hemochromatosis |
title_full_unstemmed |
Genetic disruption of NRF2 promotes the development of necroinflammation and liver fibrosis in a mouse model of HFE-hereditary hemochromatosis |
title_sort |
Genetic disruption of NRF2 promotes the development of necroinflammation and liver fibrosis in a mouse model of HFE-hereditary hemochromatosis |
author |
Duarte, T. |
author_facet |
Duarte, T. Caldas, C. Santos, A. Silva-Gomes, S. Santos-Gonçalves, A. Martins, M. Porto, G. Lopes, J. |
author_role |
author |
author2 |
Caldas, C. Santos, A. Silva-Gomes, S. Santos-Gonçalves, A. Martins, M. Porto, G. Lopes, J. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Centro Hospitalar Universitário de Santo António |
dc.contributor.author.fl_str_mv |
Duarte, T. Caldas, C. Santos, A. Silva-Gomes, S. Santos-Gonçalves, A. Martins, M. Porto, G. Lopes, J. |
dc.subject.por.fl_str_mv |
Hepatocyte Iron Macrophage Oxidative stress Sideronecrosis |
topic |
Hepatocyte Iron Macrophage Oxidative stress Sideronecrosis |
description |
In hereditary hemochromatosis, iron deposition in the liver parenchyma may lead to fibrosis, cirrhosis and hepatocellular carcinoma. Most cases are ascribed to a common mutation in the HFE gene, but the extent of clinical expression is greatly influenced by the combined action of yet unidentified genetic and/or environmental modifying factors. In mice, transcription factor NRF2 is a critical determinant of hepatocyte viability during exposure to acute dietary iron overload. We evaluated if the genetic disruption of Nrf2 would prompt the development of liver damage in Hfe(-/-) mice (an established model of human HFE-hemochromatosis). |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-09-04T17:21:55Z 2017-04 2017-04-01T00:00:00Z |
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.uri.fl_str_mv |
http://hdl.handle.net/10400.16/2180 |
url |
http://hdl.handle.net/10400.16/2180 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Redox Biol. 2017 Apr;11:157-169 2213-2317 10.1016/j.redox.2016.11.013 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799133645645021184 |