Severe ischemia-reperfusion injury induces epigenetic inactivation of LHX1 in kidney progenitor cells after kidney transplantation

Severe ischemia-reperfusion injury (IRI) causes acute and chronic kidney allograft damage. As therapeutic interventions to reduce damage are limited yet, research on how to promote kidney repair has gained significant interest. To address this question, we performed genome-wide transcriptome and epi...

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Autores: Cruzado, Josep Ma., Sola Martínez, Anna, López Pato, Miguel, Manonelles, Anna, Varela, Cristian, Setién, Fernando, Quero-Dotor, Carlos, Heald, James S., Piñeyro, David, Amaya-Garrido, Ana, Doladé, Nuria, Codina, Sergi, Couceiro, Carlos, Bolaños, Núria, Gomà, Montse, Vigués i Julià, Francesc, Merkel, Angelika, Romagnani, Paola, Berdasco, María
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/221426
Acceso en línea:https://hdl.handle.net/2445/221426
Access Level:acceso abierto
Palabra clave:Epigènesi
Diferenciació cel·lular
Proliferació cel·lular
Animals
Epigenesis
Cell diferentiation
Cell proliferation
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spelling Severe ischemia-reperfusion injury induces epigenetic inactivation of LHX1 in kidney progenitor cells after kidney transplantationCruzado, Josep Ma.Sola Martínez, AnnaLópez Pato, MiguelManonelles, AnnaVarela, CristianSetién, FernandoQuero-Dotor, CarlosHeald, James S.Piñeyro, DavidAmaya-Garrido, AnaDoladé, NuriaCodina, SergiCouceiro, CarlosBolaños, NúriaGomà, MontseVigués i Julià, FrancescMerkel, AngelikaRomagnani, PaolaBerdasco, MaríaEpigènesiDiferenciació cel·lularProliferació cel·lularAnimalsEpigenesisCell diferentiationCell proliferationAnimalsSevere ischemia-reperfusion injury (IRI) causes acute and chronic kidney allograft damage. As therapeutic interventions to reduce damage are limited yet, research on how to promote kidney repair has gained significant interest. To address this question, we performed genome-wide transcriptome and epigenome profiling in progenitor cells isolated from the urine of deceased (severe IRI) and living (mild IRI) donor human kidney transplants and identified LIM homeobox-1 (LHX1) as an epigenetically regulated gene whose expression depends on the IRI severity. Using a mouse model of IRI, we observed a relationship between IRI severity, LHX1 promoter hypermethylation, and LHX1 gene expression. Using functional studies, we confirmed that LHX1 expression is involved in the proliferation of epithelial tubular cells and podocyte differentiation from kidney progenitor cells. Our results provide evidence that severe IRI may reduce intrinsic mechanisms of kidney repair through epigenetic signaling.Wiley2025202520242025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion13 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/221426Articles publicats en revistes (Ciències Clíniques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/doi: 10.1016/j.ajt.2024.11.003American Journal of Transplantation, 2024, vol. 25, num.3, p. 476-488https://doi.org/doi: 10.1016/j.ajt.2024.11.003cc-by (c) Cruzado, Josep Ma. et al., 2024https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2214262026-05-29T05:05:01Z
dc.title.none.fl_str_mv Severe ischemia-reperfusion injury induces epigenetic inactivation of LHX1 in kidney progenitor cells after kidney transplantation
title Severe ischemia-reperfusion injury induces epigenetic inactivation of LHX1 in kidney progenitor cells after kidney transplantation
spellingShingle Severe ischemia-reperfusion injury induces epigenetic inactivation of LHX1 in kidney progenitor cells after kidney transplantation
Cruzado, Josep Ma.
Epigènesi
Diferenciació cel·lular
Proliferació cel·lular
Animals
Epigenesis
Cell diferentiation
Cell proliferation
Animals
title_short Severe ischemia-reperfusion injury induces epigenetic inactivation of LHX1 in kidney progenitor cells after kidney transplantation
title_full Severe ischemia-reperfusion injury induces epigenetic inactivation of LHX1 in kidney progenitor cells after kidney transplantation
title_fullStr Severe ischemia-reperfusion injury induces epigenetic inactivation of LHX1 in kidney progenitor cells after kidney transplantation
title_full_unstemmed Severe ischemia-reperfusion injury induces epigenetic inactivation of LHX1 in kidney progenitor cells after kidney transplantation
title_sort Severe ischemia-reperfusion injury induces epigenetic inactivation of LHX1 in kidney progenitor cells after kidney transplantation
dc.creator.none.fl_str_mv Cruzado, Josep Ma.
Sola Martínez, Anna
López Pato, Miguel
Manonelles, Anna
Varela, Cristian
Setién, Fernando
Quero-Dotor, Carlos
Heald, James S.
Piñeyro, David
Amaya-Garrido, Ana
Doladé, Nuria
Codina, Sergi
Couceiro, Carlos
Bolaños, Núria
Gomà, Montse
Vigués i Julià, Francesc
Merkel, Angelika
Romagnani, Paola
Berdasco, María
author Cruzado, Josep Ma.
author_facet Cruzado, Josep Ma.
Sola Martínez, Anna
López Pato, Miguel
Manonelles, Anna
Varela, Cristian
Setién, Fernando
Quero-Dotor, Carlos
Heald, James S.
Piñeyro, David
Amaya-Garrido, Ana
Doladé, Nuria
Codina, Sergi
Couceiro, Carlos
Bolaños, Núria
Gomà, Montse
Vigués i Julià, Francesc
Merkel, Angelika
Romagnani, Paola
Berdasco, María
author_role author
author2 Sola Martínez, Anna
López Pato, Miguel
Manonelles, Anna
Varela, Cristian
Setién, Fernando
Quero-Dotor, Carlos
Heald, James S.
Piñeyro, David
Amaya-Garrido, Ana
Doladé, Nuria
Codina, Sergi
Couceiro, Carlos
Bolaños, Núria
Gomà, Montse
Vigués i Julià, Francesc
Merkel, Angelika
Romagnani, Paola
Berdasco, María
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Epigènesi
Diferenciació cel·lular
Proliferació cel·lular
Animals
Epigenesis
Cell diferentiation
Cell proliferation
Animals
topic Epigènesi
Diferenciació cel·lular
Proliferació cel·lular
Animals
Epigenesis
Cell diferentiation
Cell proliferation
Animals
description Severe ischemia-reperfusion injury (IRI) causes acute and chronic kidney allograft damage. As therapeutic interventions to reduce damage are limited yet, research on how to promote kidney repair has gained significant interest. To address this question, we performed genome-wide transcriptome and epigenome profiling in progenitor cells isolated from the urine of deceased (severe IRI) and living (mild IRI) donor human kidney transplants and identified LIM homeobox-1 (LHX1) as an epigenetically regulated gene whose expression depends on the IRI severity. Using a mouse model of IRI, we observed a relationship between IRI severity, LHX1 promoter hypermethylation, and LHX1 gene expression. Using functional studies, we confirmed that LHX1 expression is involved in the proliferation of epithelial tubular cells and podocyte differentiation from kidney progenitor cells. Our results provide evidence that severe IRI may reduce intrinsic mechanisms of kidney repair through epigenetic signaling.
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/221426
url https://hdl.handle.net/2445/221426
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/doi: 10.1016/j.ajt.2024.11.003
American Journal of Transplantation, 2024, vol. 25, num.3, p. 476-488
https://doi.org/doi: 10.1016/j.ajt.2024.11.003
dc.rights.none.fl_str_mv cc-by (c) Cruzado, Josep Ma. et al., 2024
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Cruzado, Josep Ma. et al., 2024
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 13 p.
application/pdf
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 (Ciències Clíniques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869415797578792960
score 15,811543

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