Finerenone prevents renal damage by enhancing SDF-1α/CXCR4-mediated stem cell mobilization in experimental type 1 diabetic nephropathy
Bibliographic record
Abstract
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. • FIN exerts renoprotective effects in a rat model of T1DM. • FIN restores the canonical SDF-1α/CXCR4 signaling axis. • FIN reduces levels of the proinflammatory SDF-1α (5–67) fragment by MMP-2 and MMP-9 inhibition. • FIN promotes mobilization of CD34⁺/CXCR4⁺ hematopoietic stem cells into the renal tissue. • These benefits might translate to patients with T1DM and chronic kidney disease.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".