Akt-mediated FoxO1 inhibition is required for liver regeneration

Understanding the hepatic regenerative process has clinical interest as the effectiveness of many treatments for chronic liver diseases is conditioned by efficient liver regeneration. Experimental evidence points to the need for a temporal coordination between cytokines, growth factors, and metaboli...

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Autores: Pauta, Montse, Rotllan, Noemi, Fernández Hernando, Ana, Langhi, Cedric, Ribera Sabaté, Jordi, Boix i Ferrero, Loreto, Bruix Tudó, Jordi, Jiménez Povedano, Wladimiro, Duarez, Yajaira, Ford, David A., Baldán, Morris J., Bimbaum, Morris J., Morales Ruiz, Manuel, Fernández Hernando, Carlos
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/173239
Acesso em linha:https://hdl.handle.net/2445/173239
Access Level:acceso abierto
Palavra-chave:Regeneració (Biologia)
Fetge
Regeneration (Biology)
Liver
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repository_id_str
spelling Akt-mediated FoxO1 inhibition is required for liver regenerationPauta, MontseRotllan, NoemiFernández Hernando, AnaLanghi, CedricRibera Sabaté, JordiBoix i Ferrero, LoretoBruix Tudó, JordiJiménez Povedano, WladimiroDuarez, YajairaFord, David A.Baldán, Morris J.Bimbaum, Morris J.Morales Ruiz, ManuelFernández Hernando, CarlosRegeneració (Biologia)FetgeRegeneration (Biology)LiverUnderstanding the hepatic regenerative process has clinical interest as the effectiveness of many treatments for chronic liver diseases is conditioned by efficient liver regeneration. Experimental evidence points to the need for a temporal coordination between cytokines, growth factors, and metabolic signaling pathways to enable successful liver regeneration. One intracellular mediator that acts as a signal integration node for these processes is the serine-threonine kinase Akt/protein kinase B (Akt). To investigate the contribution of Akt during hepatic regeneration, we performed partial hepatectomy in mice lacking Akt1, Akt2, or both isoforms. We found that absence of Akt1 or Akt2 does not influence liver regeneration after partial hepatectomy. However, hepatic-specific Akt1 and Akt2 null mice show impaired liver regeneration and increased mortality. The major abnormal cellular events observed in total Akt-deficient livers were a marked reduction in cell proliferation, cell hypertrophy, glycogenesis, and lipid droplet formation. Most importantly, liver-specific deletion of FoxO1, a transcription factor regulated by Akt, rescued the hepatic regenerative capability in Akt1-deficient and Akt2- deficient mice and normalized the cellular events associated with liver regeneration. Conclusion: The Akt-FoxO1 signaling pathway plays an essential role during liver regeneration.Wiley2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/173239Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1002/hep.28286Hepatology, 2016, vol. 63, num. 5, p. 1660-1674https://doi.org/10.1002/hep.28286(c) American Association for the Study of Liver Diseases, 2016info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1732392026-05-27T06:46:51Z
dc.title.none.fl_str_mv Akt-mediated FoxO1 inhibition is required for liver regeneration
title Akt-mediated FoxO1 inhibition is required for liver regeneration
spellingShingle Akt-mediated FoxO1 inhibition is required for liver regeneration
Pauta, Montse
Regeneració (Biologia)
Fetge
Regeneration (Biology)
Liver
title_short Akt-mediated FoxO1 inhibition is required for liver regeneration
title_full Akt-mediated FoxO1 inhibition is required for liver regeneration
title_fullStr Akt-mediated FoxO1 inhibition is required for liver regeneration
title_full_unstemmed Akt-mediated FoxO1 inhibition is required for liver regeneration
title_sort Akt-mediated FoxO1 inhibition is required for liver regeneration
dc.creator.none.fl_str_mv Pauta, Montse
Rotllan, Noemi
Fernández Hernando, Ana
Langhi, Cedric
Ribera Sabaté, Jordi
Boix i Ferrero, Loreto
Bruix Tudó, Jordi
Jiménez Povedano, Wladimiro
Duarez, Yajaira
Ford, David A.
Baldán, Morris J.
Bimbaum, Morris J.
Morales Ruiz, Manuel
Fernández Hernando, Carlos
author Pauta, Montse
author_facet Pauta, Montse
Rotllan, Noemi
Fernández Hernando, Ana
Langhi, Cedric
Ribera Sabaté, Jordi
Boix i Ferrero, Loreto
Bruix Tudó, Jordi
Jiménez Povedano, Wladimiro
Duarez, Yajaira
Ford, David A.
Baldán, Morris J.
Bimbaum, Morris J.
Morales Ruiz, Manuel
Fernández Hernando, Carlos
author_role author
author2 Rotllan, Noemi
Fernández Hernando, Ana
Langhi, Cedric
Ribera Sabaté, Jordi
Boix i Ferrero, Loreto
Bruix Tudó, Jordi
Jiménez Povedano, Wladimiro
Duarez, Yajaira
Ford, David A.
Baldán, Morris J.
Bimbaum, Morris J.
Morales Ruiz, Manuel
Fernández Hernando, Carlos
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Regeneració (Biologia)
Fetge
Regeneration (Biology)
Liver
topic Regeneració (Biologia)
Fetge
Regeneration (Biology)
Liver
description Understanding the hepatic regenerative process has clinical interest as the effectiveness of many treatments for chronic liver diseases is conditioned by efficient liver regeneration. Experimental evidence points to the need for a temporal coordination between cytokines, growth factors, and metabolic signaling pathways to enable successful liver regeneration. One intracellular mediator that acts as a signal integration node for these processes is the serine-threonine kinase Akt/protein kinase B (Akt). To investigate the contribution of Akt during hepatic regeneration, we performed partial hepatectomy in mice lacking Akt1, Akt2, or both isoforms. We found that absence of Akt1 or Akt2 does not influence liver regeneration after partial hepatectomy. However, hepatic-specific Akt1 and Akt2 null mice show impaired liver regeneration and increased mortality. The major abnormal cellular events observed in total Akt-deficient livers were a marked reduction in cell proliferation, cell hypertrophy, glycogenesis, and lipid droplet formation. Most importantly, liver-specific deletion of FoxO1, a transcription factor regulated by Akt, rescued the hepatic regenerative capability in Akt1-deficient and Akt2- deficient mice and normalized the cellular events associated with liver regeneration. Conclusion: The Akt-FoxO1 signaling pathway plays an essential role during liver regeneration.
publishDate 2016
dc.date.none.fl_str_mv 2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/173239
url https://hdl.handle.net/2445/173239
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1002/hep.28286
Hepatology, 2016, vol. 63, num. 5, p. 1660-1674
https://doi.org/10.1002/hep.28286
dc.rights.none.fl_str_mv (c) American Association for the Study of Liver Diseases, 2016
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Association for the Study of Liver Diseases, 2016
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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