RT Journal Article
T1 Finerenone prevents renal damage by enhancing SDF-1α/CXCR4-mediated stem cell mobilization in experimental type 1 diabetic nephropathy
A1 Paloma Palma-Guzmán, 
A1 Elvira Bragado-García, 
A1 Esther Durán-Mateos, 
A1 Marta Sanz Gómez, 
A1 Christopher Overall, 
A1 Isabel Aranguez, 
A1 Elisa Mercado-García, 
A1 Gema Ruiz-Hurtado, 
A1 Reinhold Kreutz, 
A1 Adrián Plaza, 
A1 María S Fernández-Alfonso, 
A1 Merino Martín, José Joaquín
AB 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.
PB Elsevier
YR 2025
FD 2025
LK https://hdl.handle.net/20.500.14352/125953
UL https://hdl.handle.net/20.500.14352/125953
LA eng
NO Palma-Guzmán P, Bragado-García E, Durán-Mateos E, et al. Finerenone prevents renal damage by enhancing SDF-1α/CXCR4-mediated stem cell mobilization in experimental type 1 diabetic nephropathy. Biomedicine & Pharmacotherapy 2025;193:118727. https://doi.org/10.1016/j.biopha.2025.118727.
NO Ministerio de Economía y Competitividad (España)
NO Bayer AG
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 24 mar 2026