Finerenone prevents renal damage by enhancing SDF-1α/CXCR4-mediated stem cell mobilization in experimental type 1 diabetic nephropathy

Finerenone (FIN), a non-steroidal mineralocorticoid receptor antagonist, improves kidney and cardiovascular damage in type 1 diabetic (T1DM) Munich Wistar Frömter (MWF) rats with established chronic kidney disease (CKD). We tested whether renal protection involves stromal cell-derived factor 1 (SDF-...

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Autores: Paloma Palma-Guzmán, Elvira Bragado-García, Esther Durán-Mateos, Marta Sanz Gómez, Christopher Overall, Isabel Aranguez, Elisa Mercado-García, Gema Ruiz-Hurtado, Reinhold Kreutz, Adrián Plaza, María S Fernández-Alfonso, Merino Martín, José Joaquín
Formato: artículo
Fecha de publicación:2025
País:España
Recursos:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/125953
Acesso em linha:https://hdl.handle.net/20.500.14352/125953
Access Level:acceso abierto
Palavra-chave:615.01/.03
Type 1 diabetes
Diabetic nephropathy
Finerenone
Chemokines
Metalloproteinases
Stem cell mobilization
Farmacología (Farmacia)
3209 Farmacología
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spelling Finerenone prevents renal damage by enhancing SDF-1α/CXCR4-mediated stem cell mobilization in experimental type 1 diabetic nephropathyPaloma Palma-GuzmánElvira Bragado-GarcíaEsther Durán-MateosMarta Sanz GómezChristopher OverallIsabel AranguezElisa Mercado-GarcíaGema Ruiz-HurtadoReinhold KreutzAdrián PlazaMaría S Fernández-AlfonsoMerino Martín, José Joaquín615.01/.03Type 1 diabetesDiabetic nephropathyFinerenoneChemokinesMetalloproteinasesStem cell mobilizationFarmacología (Farmacia)3209 FarmacologíaFinerenone (FIN), a non-steroidal mineralocorticoid receptor antagonist, improves kidney and cardiovascular damage in type 1 diabetic (T1DM) Munich Wistar Frömter (MWF) rats with established chronic kidney disease (CKD). We tested whether renal protection involves stromal cell-derived factor 1 (SDF-1)/CXCR4 chemokine axis, a key regulator of tissue repair and stem cell mobilization. T1DM was induced in sixteen-week-old MWF by streptozotocin (15 mg/Kg, i.p.), combined with high fat/high sucrose (HF/HS) diet for 6 weeks (D). A second group (D-FIN) received FIN (10 mg/Kg/day) via the HF/HS diet. Non-diabetic MWF served as controls (C) (n = 11/group). Renal damage was evaluated by histology, RT-qPCR, ELISA, and zymography for matrix metalloproteinase (MMP) activity. Diabetic kidneys in group D showed enhanced glomerulosclerosis, interstitial inflammation, and elevated MMP-2 and MMP-9 activity. FIN treatment significantly reduced these changes, including tubular necrosis and collagen accumulation. Timp-1, Timp-2 and Pai-1 expression remained unchanged across groups. Notably, FIN upregulated SDF-1α and its receptor CXCR4, which are crucial for hematopoietic stem cell (HSC) migration. Conversely, SDF-1α (5-67), a truncated, non-functional form that impairs CXCR4 binding, was reduced with FIN. Immunofluorescence revealed co-localization of CXCR4 with CD34, an HSC marker, in the D-FIN group. We conclude that FIN mitigates diabetic kidney injury in MWF rats by promoting HSC (CD34⁺) recruitment to the kidney. This is mediated through decreased MMP-2/9 activity, upregulation of the SDF-1α/CXCR4 axis, and reduced expression of the non-functional SDF-1α (5-67) form. These findings support a novel mechanism of FIN-induced renal protection involving stem cell mobilization.ElsevierUniversidad Complutense de Madrid20252025-01-0120252025-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/125953reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1259532026-06-02T12:44:21Z
dc.title.none.fl_str_mv Finerenone prevents renal damage by enhancing SDF-1α/CXCR4-mediated stem cell mobilization in experimental type 1 diabetic nephropathy
title Finerenone prevents renal damage by enhancing SDF-1α/CXCR4-mediated stem cell mobilization in experimental type 1 diabetic nephropathy
spellingShingle Finerenone prevents renal damage by enhancing SDF-1α/CXCR4-mediated stem cell mobilization in experimental type 1 diabetic nephropathy
Paloma Palma-Guzmán
615.01/.03
Type 1 diabetes
Diabetic nephropathy
Finerenone
Chemokines
Metalloproteinases
Stem cell mobilization
Farmacología (Farmacia)
3209 Farmacología
title_short Finerenone prevents renal damage by enhancing SDF-1α/CXCR4-mediated stem cell mobilization in experimental type 1 diabetic nephropathy
title_full Finerenone prevents renal damage by enhancing SDF-1α/CXCR4-mediated stem cell mobilization in experimental type 1 diabetic nephropathy
title_fullStr Finerenone prevents renal damage by enhancing SDF-1α/CXCR4-mediated stem cell mobilization in experimental type 1 diabetic nephropathy
title_full_unstemmed Finerenone prevents renal damage by enhancing SDF-1α/CXCR4-mediated stem cell mobilization in experimental type 1 diabetic nephropathy
title_sort Finerenone prevents renal damage by enhancing SDF-1α/CXCR4-mediated stem cell mobilization in experimental type 1 diabetic nephropathy
dc.creator.none.fl_str_mv Paloma Palma-Guzmán
Elvira Bragado-García
Esther Durán-Mateos
Marta Sanz Gómez
Christopher Overall
Isabel Aranguez
Elisa Mercado-García
Gema Ruiz-Hurtado
Reinhold Kreutz
Adrián Plaza
María S Fernández-Alfonso
Merino Martín, José Joaquín
author Paloma Palma-Guzmán
author_facet Paloma Palma-Guzmán
Elvira Bragado-García
Esther Durán-Mateos
Marta Sanz Gómez
Christopher Overall
Isabel Aranguez
Elisa Mercado-García
Gema Ruiz-Hurtado
Reinhold Kreutz
Adrián Plaza
María S Fernández-Alfonso
Merino Martín, José Joaquín
author_role author
author2 Elvira Bragado-García
Esther Durán-Mateos
Marta Sanz Gómez
Christopher Overall
Isabel Aranguez
Elisa Mercado-García
Gema Ruiz-Hurtado
Reinhold Kreutz
Adrián Plaza
María S Fernández-Alfonso
Merino Martín, José Joaquín
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 615.01/.03
Type 1 diabetes
Diabetic nephropathy
Finerenone
Chemokines
Metalloproteinases
Stem cell mobilization
Farmacología (Farmacia)
3209 Farmacología
topic 615.01/.03
Type 1 diabetes
Diabetic nephropathy
Finerenone
Chemokines
Metalloproteinases
Stem cell mobilization
Farmacología (Farmacia)
3209 Farmacología
description Finerenone (FIN), a non-steroidal mineralocorticoid receptor antagonist, improves kidney and cardiovascular damage in type 1 diabetic (T1DM) Munich Wistar Frömter (MWF) rats with established chronic kidney disease (CKD). We tested whether renal protection involves stromal cell-derived factor 1 (SDF-1)/CXCR4 chemokine axis, a key regulator of tissue repair and stem cell mobilization. T1DM was induced in sixteen-week-old MWF by streptozotocin (15 mg/Kg, i.p.), combined with high fat/high sucrose (HF/HS) diet for 6 weeks (D). A second group (D-FIN) received FIN (10 mg/Kg/day) via the HF/HS diet. Non-diabetic MWF served as controls (C) (n = 11/group). Renal damage was evaluated by histology, RT-qPCR, ELISA, and zymography for matrix metalloproteinase (MMP) activity. Diabetic kidneys in group D showed enhanced glomerulosclerosis, interstitial inflammation, and elevated MMP-2 and MMP-9 activity. FIN treatment significantly reduced these changes, including tubular necrosis and collagen accumulation. Timp-1, Timp-2 and Pai-1 expression remained unchanged across groups. Notably, FIN upregulated SDF-1α and its receptor CXCR4, which are crucial for hematopoietic stem cell (HSC) migration. Conversely, SDF-1α (5-67), a truncated, non-functional form that impairs CXCR4 binding, was reduced with FIN. Immunofluorescence revealed co-localization of CXCR4 with CD34, an HSC marker, in the D-FIN group. We conclude that FIN mitigates diabetic kidney injury in MWF rats by promoting HSC (CD34⁺) recruitment to the kidney. This is mediated through decreased MMP-2/9 activity, upregulation of the SDF-1α/CXCR4 axis, and reduced expression of the non-functional SDF-1α (5-67) form. These findings support a novel mechanism of FIN-induced renal protection involving stem cell mobilization.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-01-01
2025
2025-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
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/20.500.14352/125953
url https://hdl.handle.net/20.500.14352/125953
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.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:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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