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...

Descripción completa

Detalles Bibliográficos
Autores: Maus, Mate, López-Polo, Vanessa, Mateo, Lidia, Lafarga Coscojuela, Miguel Ángel|||0000-0003-3402-1152, Aguilera, Mònica, Lama, Eugenia de, Meyer, Kathleen, Sola, Anna, López-Martínez, Cecilia, López-Alonso, Inés, Guasch-Piqueras, Marc, Hernández-González, Fernanda, Chaib, Selim, Rovira, Miguel, Sánchez, Mayka, Faner, Rosa, Agustí, Alvar, Diéguez-Hurtado, Rodrigo, Ortega, Sagrario, Manonelles, Anna
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad de Cantabria (UC)
Repositorio:UCrea Repositorio Abierto de la Universidad de Cantabria
Idioma:inglés
OAI Identifier:oai:repositorio.unican.es:10902/30884
Acceso en línea:https://hdl.handle.net/10902/30884
Access Level:acceso abierto
id ES_ae5f88b34ec53da7d39538825dfd9b7d
oai_identifier_str oai:repositorio.unican.es:10902/30884
network_acronym_str ES
network_name_str España
repository_id_str
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
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 Coscojuela, Miguel Ángel|||0000-0003-3402-1152
Aguilera, Mònica
Lama, Eugenia de
Meyer, Kathleen
Sola, Anna
López-Martínez, Cecilia
López-Alonso, Inés
Guasch-Piqueras, Marc
Hernández-González, Fernanda
Chaib, Selim
Rovira, Miguel
Sánchez, Mayka
Faner, Rosa
Agustí, Alvar
Diéguez-Hurtado, Rodrigo
Ortega, Sagrario
Manonelles, Anna
author Maus, Mate
author_facet Maus, Mate
López-Polo, Vanessa
Mateo, Lidia
Lafarga Coscojuela, Miguel Ángel|||0000-0003-3402-1152
Aguilera, Mònica
Lama, Eugenia de
Meyer, Kathleen
Sola, Anna
López-Martínez, Cecilia
López-Alonso, Inés
Guasch-Piqueras, Marc
Hernández-González, Fernanda
Chaib, Selim
Rovira, Miguel
Sánchez, Mayka
Faner, Rosa
Agustí, Alvar
Diéguez-Hurtado, Rodrigo
Ortega, Sagrario
Manonelles, Anna
author_role author
author2 López-Polo, Vanessa
Mateo, Lidia
Lafarga Coscojuela, Miguel Ángel|||0000-0003-3402-1152
Aguilera, Mònica
Lama, Eugenia de
Meyer, Kathleen
Sola, Anna
López-Martínez, Cecilia
López-Alonso, Inés
Guasch-Piqueras, Marc
Hernández-González, Fernanda
Chaib, Selim
Rovira, Miguel
Sánchez, Mayka
Faner, Rosa
Agustí, Alvar
Diéguez-Hurtado, Rodrigo
Ortega, Sagrario
Manonelles, Anna
author2_role 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 Universidad de Cantabria
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
2023-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10902/30884
url https://hdl.handle.net/10902/30884
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 4.0 International
http://creativecommons.org/licenses/by/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 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Nature Metabolism, 2023
reponame:UCrea Repositorio Abierto de la Universidad de Cantabria
instname:Universidad de Cantabria (UC)
instname_str Universidad de Cantabria (UC)
reponame_str UCrea Repositorio Abierto de la Universidad de Cantabria
collection UCrea Repositorio Abierto de la Universidad de Cantabria
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869416556390252544
spelling Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype.Maus, MateLópez-Polo, VanessaMateo, LidiaLafarga Coscojuela, Miguel Ángel|||0000-0003-3402-1152Aguilera, MònicaLama, Eugenia deMeyer, KathleenSola, AnnaLópez-Martínez, CeciliaLópez-Alonso, InésGuasch-Piqueras, MarcHernández-González, FernandaChaib, SelimRovira, MiguelSánchez, MaykaFaner, RosaAgustí, AlvarDiéguez-Hurtado, RodrigoOrtega, SagrarioManonelles, AnnaFibrogenesis 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.Acknowledgements: We are grateful to K. Raj (Altos Laboratories) for his help with the experiments on replicative senescence. We thank D. Muñoz Espin (University of Cambridge) for sending us the IMR90 cells stably transduced with tamoxifen inducible Ras-G12V. We thank R. Mendez (IRB) for the H5V and HUVEC cells. We thank staf at the TEM-SEM Electron Microscopy Unit from Scientific and Technological Centers (CCiTUB), Universitat de Barcelona for their support and advice on TEM techniques. We are thankful to the Magnetic Resonance Imaging Core Facility of the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) for the scientific and technical support in MRI acquisition and analysis. M.M. received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement (no. 794744) and from the Spanish Ministry of Science and Innovation (MCIN) (RYC2020-030652-I/AEI/10.13039/501100011033). V.L.P. was a recipient of a predoctoral contract from the Spanish Ministry of Education (FPU-18/05917). K.M. was a recipient of fellowships from the German Cardiac, the German Research Foundation and a postdoctoral contract Juan de la Cierva from the MCIN. F.H.G. was supported by the PhD4MD Collaborative Research Training Program for Medical Doctors (IRB Barcelona/Hospital Clinic/IDIBAPS). M. Sanchez was funded by grants PID2021- 122436OB-I00 from MCIN/AEI/10.13039/501100011033/FEDER, UE, RETOS COLABORACION RTC2019-007074-1 from MCIN/ AEI/10.13039/501100011033. C.L.-M. was a recipient of a predoctoral contract from the Spanish Ministry of Education (FPU-18/02965). G.A. was funded by the Instituto de Salud Carlos III through project PI 20/01360, FEDER funds. J.M.C. was funded by the Instituto de Salud Carlos III through projects PI18/00910 and PI21/00931 (co-funded by European Regional Development Fund, a way to build Europe) and thanks the CERCA Programme/ Generalitat de Catalunya for institutional support. Work in the laboratory of M. Serrano was funded by the IRB and ‘laCaixa’ Foundation and by grants from the Spanish Ministry of Science co-funded by the European Regional Development Fund (SAF2017- 82613-R), European Research Council (ERC-2014-AdG/669622) and grant RETOS COLABORACION RTC2019-007125-1 from MCIN/AEI and Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement of Catalonia (Grup de Recerca consolidat 2017 SGR 282)Universidad de Cantabria20232023-01-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttps://hdl.handle.net/10902/30884Nature Metabolism, 2023reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.unican.es:10902/308842026-06-02T12:39:31Z
score 15,300719

Similares en LA Referencia