NGAL release from peripheral blood mononuclear cells protects against acute kidney injury and prevents AKI induced fibrosis

We propose the use of a peripheral blood mononuclear cell therapy based on cell NGAL release to be used in the clinical setting for acute kidney injury (AKI) and the derived fibrosis. First, we designed a procedure whereby PBMC overexpress NGAL and anti-inflammatory agents when subjected to repetiti...

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Detalles Bibliográficos
Autores: Játiva, Soraya, Torrico, Selene, Calle, Priscila, Muñoz, Ángeles, García, Miriam R., Larque, Ana Belén, Poch, Esteban, Hotter, Georgina
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/304416
Acceso en línea:http://hdl.handle.net/10261/304416
Access Level:acceso abierto
Palabra clave:Macrophage
Monocyte
Acute kidney failure
Inflammation
NGAL
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spelling NGAL release from peripheral blood mononuclear cells protects against acute kidney injury and prevents AKI induced fibrosisJátiva, SorayaTorrico, SeleneCalle, PriscilaMuñoz, ÁngelesGarcía, Miriam R.Larque, Ana BelénPoch, EstebanHotter, GeorginaMacrophageMonocyteAcute kidney failureInflammationNGALWe propose the use of a peripheral blood mononuclear cell therapy based on cell NGAL release to be used in the clinical setting for acute kidney injury (AKI) and the derived fibrosis. First, we designed a procedure whereby PBMC overexpress NGAL and anti-inflammatory agents when subjected to repetitive anoxia/reoxygenation (PBMC (A/R)). Using an in vivo AKI model, we observed that PBMC(A/R) reduces BUN and creatinine levels in blood and inflammation, enhances anti-inflammation, induces proliferation of tubular epithelial cells and reduces AKI-induced fibrosis. Flow cytometry analysis evidenced that monocytes are the only cells accumulated in the injured kidney and phenotype analysis of freshly isolated kidney macrophages, revealed that the healing phenotype is maintained the time needed for recovery. NGAL release from PBMC(A/R) determines the beneficial effect of the therapy since administration of a NGAL antibody previous to the therapy or injection of PBMC(A/R) obtained from NGAL KO animals abolished the beneficial effects. CD11b–NGAL positive cells were enhanced in tissue after PBMC (A/R) therapy and were produced by the injected monocytes. In an in vitro model with tubular epithelial cells (NRK52e) we proved that NGAL release by PBMC(A/R) induced epithelial proliferation and activation of PI3K/Akt pathway.This research was funded by grants RTC2019-0079197-1 funded by Ministerio de Ciencia e Innovacion/Agencia ´ Estatal de Investigacion ´ MCIN/AEI/10.13039/501100011033, awarded to G.H and grant PI20/ 00900 funded by Fondo de Investigacion ´ Sanitaria (FIS), awarded to G. H.ElsevierMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2023202320222023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/304416reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI//RTC2019-0079197-1The underlying dataset has been published as supplementary material of the article in the publisher platform at 10.1016/j.biopha.2022.113415http://dx.doi.org/10.1016/j.biopha.2022.113415Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3044162026-05-22T06:33:51Z
dc.title.none.fl_str_mv NGAL release from peripheral blood mononuclear cells protects against acute kidney injury and prevents AKI induced fibrosis
title NGAL release from peripheral blood mononuclear cells protects against acute kidney injury and prevents AKI induced fibrosis
spellingShingle NGAL release from peripheral blood mononuclear cells protects against acute kidney injury and prevents AKI induced fibrosis
Játiva, Soraya
Macrophage
Monocyte
Acute kidney failure
Inflammation
NGAL
title_short NGAL release from peripheral blood mononuclear cells protects against acute kidney injury and prevents AKI induced fibrosis
title_full NGAL release from peripheral blood mononuclear cells protects against acute kidney injury and prevents AKI induced fibrosis
title_fullStr NGAL release from peripheral blood mononuclear cells protects against acute kidney injury and prevents AKI induced fibrosis
title_full_unstemmed NGAL release from peripheral blood mononuclear cells protects against acute kidney injury and prevents AKI induced fibrosis
title_sort NGAL release from peripheral blood mononuclear cells protects against acute kidney injury and prevents AKI induced fibrosis
dc.creator.none.fl_str_mv Játiva, Soraya
Torrico, Selene
Calle, Priscila
Muñoz, Ángeles
García, Miriam R.
Larque, Ana Belén
Poch, Esteban
Hotter, Georgina
author Játiva, Soraya
author_facet Játiva, Soraya
Torrico, Selene
Calle, Priscila
Muñoz, Ángeles
García, Miriam R.
Larque, Ana Belén
Poch, Esteban
Hotter, Georgina
author_role author
author2 Torrico, Selene
Calle, Priscila
Muñoz, Ángeles
García, Miriam R.
Larque, Ana Belén
Poch, Esteban
Hotter, Georgina
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Macrophage
Monocyte
Acute kidney failure
Inflammation
NGAL
topic Macrophage
Monocyte
Acute kidney failure
Inflammation
NGAL
description We propose the use of a peripheral blood mononuclear cell therapy based on cell NGAL release to be used in the clinical setting for acute kidney injury (AKI) and the derived fibrosis. First, we designed a procedure whereby PBMC overexpress NGAL and anti-inflammatory agents when subjected to repetitive anoxia/reoxygenation (PBMC (A/R)). Using an in vivo AKI model, we observed that PBMC(A/R) reduces BUN and creatinine levels in blood and inflammation, enhances anti-inflammation, induces proliferation of tubular epithelial cells and reduces AKI-induced fibrosis. Flow cytometry analysis evidenced that monocytes are the only cells accumulated in the injured kidney and phenotype analysis of freshly isolated kidney macrophages, revealed that the healing phenotype is maintained the time needed for recovery. NGAL release from PBMC(A/R) determines the beneficial effect of the therapy since administration of a NGAL antibody previous to the therapy or injection of PBMC(A/R) obtained from NGAL KO animals abolished the beneficial effects. CD11b–NGAL positive cells were enhanced in tissue after PBMC (A/R) therapy and were produced by the injected monocytes. In an in vitro model with tubular epithelial cells (NRK52e) we proved that NGAL release by PBMC(A/R) induced epithelial proliferation and activation of PI3K/Akt pathway.
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
2023
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/10261/304416
url http://hdl.handle.net/10261/304416
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI//RTC2019-0079197-1
The underlying dataset has been published as supplementary material of the article in the publisher platform at 10.1016/j.biopha.2022.113415
http://dx.doi.org/10.1016/j.biopha.2022.113415
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
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
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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