Colony stimulating factor-1 receptor drives glomerular parietal epithelial cell activation in focal segmental glomerulosclerosis

Parietal epithelial cells (PECs) are kidney progenitor cells with similarities to a bone marrow stem cell niche. In focal segmental glomerulosclerosis (FSGS) PECs become activated and contribute to extracellular matrix deposition. Colony stimulating factor-1 (CSF-1), a hematopoietic growth factor, a...

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Autores: Cruzado, Josep Ma., Manonelles, Anna, Rayego Mateos, Sandra, Doladé, Nuria, Amaya-Garrido, Ana, Varela, Cristian, Guiteras, Roser, Mosquera Mayo, José Luís, Jung, Michaela, Codina, Sergi, Martinez Valenzuela, Laura, Bordignon Draibe, Juliana, Couceiro, Carlos, Vigués i Julià, Francesc, Madrid, Álvaro, Florian, Maria Carolina, Ruíz-Ortega, Marta, Sola Martínez, Anna
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/215815
Acceso en línea:https://hdl.handle.net/2445/215815
Access Level:acceso abierto
Palabra clave:Cèl·lules epitelials
Animals
Proliferació cel·lular
Epithelial cells
Cell proliferation
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spelling Colony stimulating factor-1 receptor drives glomerular parietal epithelial cell activation in focal segmental glomerulosclerosisCruzado, Josep Ma.Manonelles, AnnaRayego Mateos, SandraDoladé, NuriaAmaya-Garrido, AnaVarela, CristianGuiteras, RoserMosquera Mayo, José LuísJung, MichaelaCodina, SergiMartinez Valenzuela, LauraBordignon Draibe, JulianaCouceiro, CarlosVigués i Julià, FrancescMadrid, ÁlvaroFlorian, Maria CarolinaRuíz-Ortega, MartaSola Martínez, AnnaCèl·lules epitelialsAnimalsProliferació cel·lularEpithelial cellsAnimalsCell proliferationParietal epithelial cells (PECs) are kidney progenitor cells with similarities to a bone marrow stem cell niche. In focal segmental glomerulosclerosis (FSGS) PECs become activated and contribute to extracellular matrix deposition. Colony stimulating factor-1 (CSF-1), a hematopoietic growth factor, acts via its specific receptor, CSF-1R, and has been implicated in several glomerular diseases, although its role on PEC activation is unknown. Here, we found that CSF-1R was upregulated in PECs and podocytes in biopsies from patients with FSGS. Through in vitro studies, PECs were found to constitutively express CSF-1R. Incubation with CSF-1 induced CSF-1R upregulation and significant transcriptional regulation of genes involved in pathways associated with PEC activation. Specifically, CSF-1/CSF-1R activated the ERK1/2 signaling pathway and upregulated CD44 in PECs, while both ERK and CSF-1R inhibitors reduced CD44 expression. Functional studies showed that CSF-1 induced PEC proliferation and migration, while reducing the differentiation of PECs into podocytes. These results were validated in the Adriamycin-induced FSGS experimental mouse model. Importantly, treatment with either the CSF-1R-specific inhibitor GW2580 or Ki20227 provided a robust therapeutic effect. Thus, we provide evidence of the role of the CSF-1/CSF-1R pathway in PEC activation in FSGS, paving the way for future clinical studies investigating the therapeutic effect of CSF-1R inhibitors on patients with FSGS.Elsevier B.V.2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/215815Articles publicats en revistes (Ciències Clíniques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1016/j.kint.2024.02.010Kidney International, 2024, vol. 106, p. 67-84https://doi.org/10.1016/j.kint.2024.02.010cc-by-nc-nd (c) Cruzado, Josep Ma. et al., 2024http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2158152026-05-27T06:46:51Z
dc.title.none.fl_str_mv Colony stimulating factor-1 receptor drives glomerular parietal epithelial cell activation in focal segmental glomerulosclerosis
title Colony stimulating factor-1 receptor drives glomerular parietal epithelial cell activation in focal segmental glomerulosclerosis
spellingShingle Colony stimulating factor-1 receptor drives glomerular parietal epithelial cell activation in focal segmental glomerulosclerosis
Cruzado, Josep Ma.
Cèl·lules epitelials
Animals
Proliferació cel·lular
Epithelial cells
Animals
Cell proliferation
title_short Colony stimulating factor-1 receptor drives glomerular parietal epithelial cell activation in focal segmental glomerulosclerosis
title_full Colony stimulating factor-1 receptor drives glomerular parietal epithelial cell activation in focal segmental glomerulosclerosis
title_fullStr Colony stimulating factor-1 receptor drives glomerular parietal epithelial cell activation in focal segmental glomerulosclerosis
title_full_unstemmed Colony stimulating factor-1 receptor drives glomerular parietal epithelial cell activation in focal segmental glomerulosclerosis
title_sort Colony stimulating factor-1 receptor drives glomerular parietal epithelial cell activation in focal segmental glomerulosclerosis
dc.creator.none.fl_str_mv Cruzado, Josep Ma.
Manonelles, Anna
Rayego Mateos, Sandra
Doladé, Nuria
Amaya-Garrido, Ana
Varela, Cristian
Guiteras, Roser
Mosquera Mayo, José Luís
Jung, Michaela
Codina, Sergi
Martinez Valenzuela, Laura
Bordignon Draibe, Juliana
Couceiro, Carlos
Vigués i Julià, Francesc
Madrid, Álvaro
Florian, Maria Carolina
Ruíz-Ortega, Marta
Sola Martínez, Anna
author Cruzado, Josep Ma.
author_facet Cruzado, Josep Ma.
Manonelles, Anna
Rayego Mateos, Sandra
Doladé, Nuria
Amaya-Garrido, Ana
Varela, Cristian
Guiteras, Roser
Mosquera Mayo, José Luís
Jung, Michaela
Codina, Sergi
Martinez Valenzuela, Laura
Bordignon Draibe, Juliana
Couceiro, Carlos
Vigués i Julià, Francesc
Madrid, Álvaro
Florian, Maria Carolina
Ruíz-Ortega, Marta
Sola Martínez, Anna
author_role author
author2 Manonelles, Anna
Rayego Mateos, Sandra
Doladé, Nuria
Amaya-Garrido, Ana
Varela, Cristian
Guiteras, Roser
Mosquera Mayo, José Luís
Jung, Michaela
Codina, Sergi
Martinez Valenzuela, Laura
Bordignon Draibe, Juliana
Couceiro, Carlos
Vigués i Julià, Francesc
Madrid, Álvaro
Florian, Maria Carolina
Ruíz-Ortega, Marta
Sola Martínez, Anna
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cèl·lules epitelials
Animals
Proliferació cel·lular
Epithelial cells
Animals
Cell proliferation
topic Cèl·lules epitelials
Animals
Proliferació cel·lular
Epithelial cells
Animals
Cell proliferation
description Parietal epithelial cells (PECs) are kidney progenitor cells with similarities to a bone marrow stem cell niche. In focal segmental glomerulosclerosis (FSGS) PECs become activated and contribute to extracellular matrix deposition. Colony stimulating factor-1 (CSF-1), a hematopoietic growth factor, acts via its specific receptor, CSF-1R, and has been implicated in several glomerular diseases, although its role on PEC activation is unknown. Here, we found that CSF-1R was upregulated in PECs and podocytes in biopsies from patients with FSGS. Through in vitro studies, PECs were found to constitutively express CSF-1R. Incubation with CSF-1 induced CSF-1R upregulation and significant transcriptional regulation of genes involved in pathways associated with PEC activation. Specifically, CSF-1/CSF-1R activated the ERK1/2 signaling pathway and upregulated CD44 in PECs, while both ERK and CSF-1R inhibitors reduced CD44 expression. Functional studies showed that CSF-1 induced PEC proliferation and migration, while reducing the differentiation of PECs into podocytes. These results were validated in the Adriamycin-induced FSGS experimental mouse model. Importantly, treatment with either the CSF-1R-specific inhibitor GW2580 or Ki20227 provided a robust therapeutic effect. Thus, we provide evidence of the role of the CSF-1/CSF-1R pathway in PEC activation in FSGS, paving the way for future clinical studies investigating the therapeutic effect of CSF-1R inhibitors on patients with FSGS.
publishDate 2024
dc.date.none.fl_str_mv 2024
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/2445/215815
url https://hdl.handle.net/2445/215815
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/10.1016/j.kint.2024.02.010
Kidney International, 2024, vol. 106, p. 67-84
https://doi.org/10.1016/j.kint.2024.02.010
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Cruzado, Josep Ma. et al., 2024
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Cruzado, Josep Ma. et al., 2024
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier B.V.
publisher.none.fl_str_mv Elsevier B.V.
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Clíniques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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