Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype.
Fibrogenesis is part of a normal protective response to tissue injury that can become irreversible and progressive, leading to fatal diseases. Senescent cells are a main driver of fibrotic diseases through their secretome, known as senescence-associated secretory phenotype (SASP). Here, we report th...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/23100 |
| Acceso en línea: | https://hdl.handle.net/20.500.12105/23100 |
| Access Level: | acceso abierto |
| Palabra clave: | Senescence-Associated Secretory Phenotype Cellular Senescence Humans Iron Kidney Fibrosis |
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Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype.Maus, MateLópez-Polo, VanessaMateo, LidiaLafarga, MiguelAguilera, MónicaDe Lama, EugeniaMeyer, KathleenSola, AnnaLopez-Martinez, CeciliaLópez-Alonso, InesGuasch-Piqueras, MarcHernandez-Gonzalez, FernandaChaib, SelimRovira, MiguelSanchez, MaykaFaner, RosaAgusti, AlvarDiéguez-Hurtado, RodrigoOrtega Jimenez, SagrarioManonelles, AnnaEngelhardt, StefanMonteiro, FreddyStephan-Otto Attolini, CamillePrats, NeusAlbaiceta, GuillermoCruzado, Josep MSerrano, ManuelSenescence-Associated Secretory PhenotypeCellular SenescenceHumansIronKidneyFibrosisFibrogenesis is part of a normal protective response to tissue injury that can become irreversible and progressive, leading to fatal diseases. Senescent cells are a main driver of fibrotic diseases through their secretome, known as senescence-associated secretory phenotype (SASP). Here, we report that cellular senescence, and multiple types of fibrotic diseases in mice and humans are characterized by the accumulation of iron. We show that vascular and hemolytic injuries are efficient in triggering iron accumulation, which in turn can cause senescence and promote fibrosis. Notably, we find that senescent cells persistently accumulate iron, even when the surge of extracellular iron has subdued. Indeed, under normal conditions of extracellular iron, cells exposed to different types of senescence-inducing insults accumulate abundant ferritin-bound iron, mostly within lysosomes, and present high levels of labile iron, which fuels the generation of reactive oxygen species and the SASP. Finally, we demonstrate that detection of iron by magnetic resonance imaging might allow non-invasive assessment of fibrotic burden in the kidneys of mice and in patients with renal fibrosis. Our findings suggest that iron accumulation plays a central role in senescence and fibrosis, even when the initiating events may be independent of iron, and identify iron metabolism as a potential therapeutic target for senescence-associated diseases.Nature Publishing GroupUnión EuropeaMinisterio de Ciencia, Innovación y Universidades (España)Instituto de Salud Carlos IIIGerman Research Foundation (DFG)20242024-09-1620232023-12-0120232023-12-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articlehttps://hdl.handle.net/20.500.12105/23100reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/231002026-06-12T12:43:37Z |
| dc.title.none.fl_str_mv |
Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype. |
| title |
Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype. |
| spellingShingle |
Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype. Maus, Mate Senescence-Associated Secretory Phenotype Cellular Senescence Humans Iron Kidney Fibrosis |
| title_short |
Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype. |
| title_full |
Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype. |
| title_fullStr |
Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype. |
| title_full_unstemmed |
Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype. |
| title_sort |
Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype. |
| dc.creator.none.fl_str_mv |
Maus, Mate López-Polo, Vanessa Mateo, Lidia Lafarga, Miguel Aguilera, Mónica De Lama, Eugenia Meyer, Kathleen Sola, Anna Lopez-Martinez, Cecilia López-Alonso, Ines Guasch-Piqueras, Marc Hernandez-Gonzalez, Fernanda Chaib, Selim Rovira, Miguel Sanchez, Mayka Faner, Rosa Agusti, Alvar Diéguez-Hurtado, Rodrigo Ortega Jimenez, Sagrario Manonelles, Anna Engelhardt, Stefan Monteiro, Freddy Stephan-Otto Attolini, Camille Prats, Neus Albaiceta, Guillermo Cruzado, Josep M Serrano, Manuel |
| author |
Maus, Mate |
| author_facet |
Maus, Mate López-Polo, Vanessa Mateo, Lidia Lafarga, Miguel Aguilera, Mónica De Lama, Eugenia Meyer, Kathleen Sola, Anna Lopez-Martinez, Cecilia López-Alonso, Ines Guasch-Piqueras, Marc Hernandez-Gonzalez, Fernanda Chaib, Selim Rovira, Miguel Sanchez, Mayka Faner, Rosa Agusti, Alvar Diéguez-Hurtado, Rodrigo Ortega Jimenez, Sagrario Manonelles, Anna Engelhardt, Stefan Monteiro, Freddy Stephan-Otto Attolini, Camille Prats, Neus Albaiceta, Guillermo Cruzado, Josep M Serrano, Manuel |
| author_role |
author |
| author2 |
López-Polo, Vanessa Mateo, Lidia Lafarga, Miguel Aguilera, Mónica De Lama, Eugenia Meyer, Kathleen Sola, Anna Lopez-Martinez, Cecilia López-Alonso, Ines Guasch-Piqueras, Marc Hernandez-Gonzalez, Fernanda Chaib, Selim Rovira, Miguel Sanchez, Mayka Faner, Rosa Agusti, Alvar Diéguez-Hurtado, Rodrigo Ortega Jimenez, Sagrario Manonelles, Anna Engelhardt, Stefan Monteiro, Freddy Stephan-Otto Attolini, Camille Prats, Neus Albaiceta, Guillermo Cruzado, Josep M Serrano, Manuel |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Unión Europea Ministerio de Ciencia, Innovación y Universidades (España) Instituto de Salud Carlos III German Research Foundation (DFG) |
| dc.subject.none.fl_str_mv |
Senescence-Associated Secretory Phenotype Cellular Senescence Humans Iron Kidney Fibrosis |
| topic |
Senescence-Associated Secretory Phenotype Cellular Senescence Humans Iron Kidney Fibrosis |
| description |
Fibrogenesis is part of a normal protective response to tissue injury that can become irreversible and progressive, leading to fatal diseases. Senescent cells are a main driver of fibrotic diseases through their secretome, known as senescence-associated secretory phenotype (SASP). Here, we report that cellular senescence, and multiple types of fibrotic diseases in mice and humans are characterized by the accumulation of iron. We show that vascular and hemolytic injuries are efficient in triggering iron accumulation, which in turn can cause senescence and promote fibrosis. Notably, we find that senescent cells persistently accumulate iron, even when the surge of extracellular iron has subdued. Indeed, under normal conditions of extracellular iron, cells exposed to different types of senescence-inducing insults accumulate abundant ferritin-bound iron, mostly within lysosomes, and present high levels of labile iron, which fuels the generation of reactive oxygen species and the SASP. Finally, we demonstrate that detection of iron by magnetic resonance imaging might allow non-invasive assessment of fibrotic burden in the kidneys of mice and in patients with renal fibrosis. Our findings suggest that iron accumulation plays a central role in senescence and fibrosis, even when the initiating events may be independent of iron, and identify iron metabolism as a potential therapeutic target for senescence-associated diseases. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023 2023-12-01 2023 2023-12-01 2024 2024-09-16 |
| dc.type.none.fl_str_mv |
research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/20.500.12105/23100 |
| url |
https://hdl.handle.net/20.500.12105/23100 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| eu_rights_str_mv |
openAccess |
| dc.publisher.none.fl_str_mv |
Nature Publishing Group |
| publisher.none.fl_str_mv |
Nature Publishing Group |
| dc.source.none.fl_str_mv |
reponame:Repisalud instname:Instituto de Salud Carlos III (ISCIII) |
| instname_str |
Instituto de Salud Carlos III (ISCIII) |
| reponame_str |
Repisalud |
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Repisalud |
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|
| repository.mail.fl_str_mv |
|
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1869425278910988288 |
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15,811543 |