Chaperone-mediated autophagy sustains pericyte stemness necessary for brain tissue homeostasis

The original contributions presented in the study are publicly available in ENA under accession number PRJEB48545.

Detalles Bibliográficos
Autores: Salinas, María Dolores, Martínez, Carlos M., Roca, Francisco J., García-Bernal, David, Martínez-Morga, Marta, Rodríguez-Madoz, Juan R., Prósper, Felipe, Zapata, Agustín, Moraleda, José María, Martínez, Salvador, Valdor, Ruth
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:dnet:digitalcsic_::d44f339db22d5bc38ec08701de37014c
Acceso en línea:http://hdl.handle.net/10261/426324
Access Level:acceso abierto
Palabra clave:Chaperone-mediated autophagy
Inflammatory damage
Injury
Pericytes as functional mesenchymal stem cells
Secretome
IFNγ
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network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Chaperone-mediated autophagy sustains pericyte stemness necessary for brain tissue homeostasis
title Chaperone-mediated autophagy sustains pericyte stemness necessary for brain tissue homeostasis
spellingShingle Chaperone-mediated autophagy sustains pericyte stemness necessary for brain tissue homeostasis
Salinas, María Dolores
Chaperone-mediated autophagy
Inflammatory damage
Injury
Pericytes as functional mesenchymal stem cells
Secretome
IFNγ
title_short Chaperone-mediated autophagy sustains pericyte stemness necessary for brain tissue homeostasis
title_full Chaperone-mediated autophagy sustains pericyte stemness necessary for brain tissue homeostasis
title_fullStr Chaperone-mediated autophagy sustains pericyte stemness necessary for brain tissue homeostasis
title_full_unstemmed Chaperone-mediated autophagy sustains pericyte stemness necessary for brain tissue homeostasis
title_sort Chaperone-mediated autophagy sustains pericyte stemness necessary for brain tissue homeostasis
dc.creator.none.fl_str_mv Salinas, María Dolores
Martínez, Carlos M.
Roca, Francisco J.
García-Bernal, David
Martínez-Morga, Marta
Rodríguez-Madoz, Juan R.
Prósper, Felipe
Zapata, Agustín
Moraleda, José María
Martínez, Salvador
Valdor, Ruth
author Salinas, María Dolores
author_facet Salinas, María Dolores
Martínez, Carlos M.
Roca, Francisco J.
García-Bernal, David
Martínez-Morga, Marta
Rodríguez-Madoz, Juan R.
Prósper, Felipe
Zapata, Agustín
Moraleda, José María
Martínez, Salvador
Valdor, Ruth
author_role author
author2 Martínez, Carlos M.
Roca, Francisco J.
García-Bernal, David
Martínez-Morga, Marta
Rodríguez-Madoz, Juan R.
Prósper, Felipe
Zapata, Agustín
Moraleda, José María
Martínez, Salvador
Valdor, Ruth
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Fundación Séneca
European Commission
Consejo Superior de Investigaciones Científicas (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Ministerio de Ciencia e Innovación (España)
Fundación la Caixa
Instituto de Salud Carlos III
Valdor, Ruth [0000-0002-2681-0779]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Chaperone-mediated autophagy
Inflammatory damage
Injury
Pericytes as functional mesenchymal stem cells
Secretome
IFNγ
topic Chaperone-mediated autophagy
Inflammatory damage
Injury
Pericytes as functional mesenchymal stem cells
Secretome
IFNγ
description The original contributions presented in the study are publicly available in ENA under accession number PRJEB48545.
publishDate 2026
dc.date.none.fl_str_mv 2026
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/426324
url http://hdl.handle.net/10261/426324
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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info:eu-repo/grantAgreement/AEI//RYC2019-027520-I
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-114010RB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-149111OB-I00
info:eu-repo/grantAgreement/AEI//RYC2019-571-027799-I
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1016/j.jare.2025.04.015
Sí
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dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
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spelling Chaperone-mediated autophagy sustains pericyte stemness necessary for brain tissue homeostasisSalinas, María DoloresMartínez, Carlos M.Roca, Francisco J.García-Bernal, DavidMartínez-Morga, MartaRodríguez-Madoz, Juan R.Prósper, FelipeZapata, AgustínMoraleda, José MaríaMartínez, SalvadorValdor, RuthChaperone-mediated autophagyInflammatory damageInjuryPericytes as functional mesenchymal stem cellsSecretomeIFNγThe original contributions presented in the study are publicly available in ENA under accession number PRJEB48545.[Introduction] Pericytes (PCs) are mural cells exhibiting some mesenchymal stem cell (MSC) properties and contribute to tissue regeneration after injury. We have previously shown that glioblastoma cancer cells induce in PCs, a pathogenic upregulation of chaperone-mediated autophagy (CMA) which modulates immune functions and MSC-like properties to support tumor growth.[Objectives] The aim of the study was to interrogate the role of CMA-regulated MSC properties in PCs in the context of tissue repair during inflammation triggered by a demyelinating injury.[Methods] Studies of RNA-seq were done PCs with (WT) and without (LAMP-2A KO) CMA. Cell characterization related to stemness, lineage and morphology was done in WT and KO PCs. Secretome analysis and cell differentiation assay using the supernatants from CMA-efficient and deficient PCs cultures was done in mesenchymal cells. Inflammatory response of brain cells was assessed with WT and KO PCs secretome. To corroborate in vitro results, CMA modulation in response to inflammation in PCs and tissue repair markers were measured in the lesion areas of a demyelination mouse model and correlated with the tissue reparation after intravenous PC administration. An inflammatory mediator was used to study effects on PC-CMA activity.[Results] We found that inflammatory mediators such as IFNγ downregulate CMA in PCs, suppressing PC stemness and promoting a pro-inflammatory secretome. Restoration of PC CMA activity during inflammation maintains PC MSC properties and induces an MSC-like proteome which decreases inflammation and promotes tissue repair. We identified secreted proteins involved in regenerative and protective processes, and therefore, necessary to restore brain tissue homeostasis after inflammation induced by a demyelinating injury.[Conclusion] we show that manipulation of CMA activity in host PCs could be a useful therapeutical approach in the context of brain inflammation, which might be extended to other diseases where the pericyte has a key role in response to inflammation.This work was mainly developed by Seneca 20840/PI/18 funded by Seneca Foundation “Agencia de Ciencia y Tecnología de la Región de Murcia”, by Ramon y Cajal (RYC) 2019-027520-I funded by Ministerio de Ciencia, Innovación y Universidades (MCIU) and Agencia Estatal de Investigación (AEI) MCIU/AEI/10.13039/501100011033, as “ European Social Fund (ESF) Investing in your future”, and by PID2020-114010RB-I00 and PID2023-149111OB-I00 funded by MICIU/AEI/10.13039/50110001 1033 and Fondo Europeo de Desarrollo Regional (FEDER), UE (to RV). It was also partially supported by CaixaImpulse CI23-20487 funded by ¨La Caixa¨ Foundation (to RV) and by Spanish Network of Advanced Therapies (TERAV), RICORS subprogram (to AGZ, FP, SM and JMM), funded by Instituto de Salud Carlos III and co-funded by European Regional Development Fund (ERDF)-Next Generation EU “Plan de Recuperación, Transformación y Resiliencia”. FJR was supported by fellowship RYC2019-571 027799-I funded by MCIU/AEI.Peer reviewedElsevierFundación SénecaEuropean CommissionConsejo Superior de Investigaciones Científicas (España)Ministerio de Ciencia, Innovación y Universidades (España)Ministerio de Ciencia e Innovación (España)Fundación la CaixaInstituto de Salud Carlos IIIValdor, Ruth [0000-0002-2681-0779]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202620262026info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/426324reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI//RYC2019-027520-Iinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-114010RB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-149111OB-I00info:eu-repo/grantAgreement/AEI//RYC2019-571-027799-IThe underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1016/j.jare.2025.04.015Síinfo:eu-repo/semantics/openAccessoai:dnet:digitalcsic_::d44f339db22d5bc38ec08701de37014c2026-05-22T06:33:51Z
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