%0 Journal Article
%A Paloma Palma-Guzmán
%A Elvira Bragado-García
%A Esther Durán-Mateos
%A Marta Sanz Gómez
%A Christopher Overall
%A Isabel Aranguez
%A Elisa Mercado-García
%A Gema Ruiz-Hurtado
%A Reinhold Kreutz
%A Adrián Plaza
%A María S Fernández-Alfonso
%A Merino Martín, José Joaquín
%T Finerenone prevents renal damage by enhancing SDF-1α/CXCR4-mediated stem cell mobilization in experimental type 1 diabetic nephropathy
%D 2025
%U https://hdl.handle.net/20.500.14352/125953
%X 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.
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