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oai:docta.ucm.es:20.500.14352/1259532025-11-13T00:56:04Zcom_20.500.14352_14col_20.500.14352_15

Finerenone prevents renal damage by enhancing SDF-1α/CXCR4-mediated stem cell mobilization in experimental type 1 diabetic nephropathy 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 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. 2025-11-11T10:50:53Z 2025-11-11T10:50:53Z 2025 journal article 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. 10.1016/j.biopha.2025.118727 https://hdl.handle.net/20.500.14352/125953 https://doi.org/10.1016/j.biopha.2025.118727 https://pubmed.ncbi.nlm.nih.gov/41191984/ eng PID2022–137116OB-I00 GR-921641 http://creativecommons.org/licenses/by/4.0/ open access Attribution 4.0 International Elsevier