Mesenchymal Stem Cells and Empagliflozin: a potential therapeutic approach for autophagy and Klotho modulation in Diabetic Kidney Disease

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ID: 323189
2026
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Abstract
Diabetic kidney disease (DKD), the leading cause of end-stage renal disease, involves injury across multiple renal compartments. Autophagy dysregulation is a key pathogenic mechanism and may reduce Klotho, a renoprotective protein diminished in DKD. This study evaluated whether bone marrow-derived mesenchymal stem cells (MSCs), combined with empagliflozin and calorie restriction, could modulate autophagy and preserve Klotho expression in DKD. Male BTBRob/ob mice, a leptin-deficient model that develops diabetes and DKD in a progressive manner, were assigned to experimental groups and euthanized at 14-15 or 18-20 weeks. Kidney tissues were analyzed by qPCR, Western blot, and immunohistochemistry. MSCs therapy improved hyperglycemia in a time-dependent manner (p < 0.0001), decreased albuminuria, and modestly improved eGFR, though weight gain persisted. Treatment modulated LC3 protein expression in cortical and medullary regions (p < 0.05), suggesting attenuation of early autophagy hyperactivation. It also helped maintain Klotho expression, correlating with reduced oxidative stress (p < 0.05). Overall, MSCs combined with empagliflozin and calorie restriction show promise as a translational approach for DKD, warranting further long-term preclinical studies.
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openalex_W7172099598 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Marcella Liciani Franco, Stephany Beyerstedt, Bruno Sérgio Toledo Barbosa, Tuany R Alves, Andrei F. Da Silva, Melise Oliveira Mariano, Alanah K Carlos, Jaqueline Arjona, Gleice Regina Josefi-Rocha, Rosana Maria Cardoso de Bastos¹, Érika B Rangel
Journal stem cells international
Year 2026
DOI
10.1093/stmcls/sxag043
URL
https://doi.org/10.1093/stmcls/sxag043
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