Distinct Temporal Modulation of Mesenchymal Stem Cells and Empagliflozin on Renal c-Kit Cells in Diabetic Kidney Disease
Abstract
Background: Diabetic kidney disease (DKD) remains a leading cause of chronic kidney disease worldwide despite current standard therapies. c-Kit+ renal progenitor cells have been implicated in kidney repair and regeneration. We investigated whether mesenchymal stem cells (MSCs) and the sodium-glucose cotransporter-2 inhibitor empagliflozin are associated with differential modulation of intrarenal c-Kit+ cell expression in a preclinical model of DKD using BTBRob/ob mice.
Methods: These BTBRob/ob mice were allocated into three groups: untreated DKD, MSC-treated DKD, and empagliflozin-treated DKD, and were compared with BTBR wild-type (WT) controls. BTBRob/ob mice received empagliflozin formulated inchow ad libitum at 25 mg/kg (Jardiance®, Boehringer Ingelheim, Ingelheim am Rhein, RP, Germany) starting at 4-5 weeks of age. MSCs (1 × 106 cells per dose) were administered intraperitoneally at 8 and 10 weeks of age. Animals were evaluated at 10, 14-15, and 18-20 weeks. Renal c-Kit gene expression was quantified by quantitative real-time PCR (qPCR), and protein expression was assessed by immunohistochemistry in the cortex, medulla, and glomeruli. Statistical analyses included mixed-effects models and two-way analysis of variance (ANOVA).
Results: c-Kit expression was significantly influenced by time and treatment in both cortex and medulla. In the renal cortex, MSC therapy was associated with a transient increase in c-Kit gene expression at 14-15 weeks, followed by a reduction at…
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