Mesenchymal Stem Cells and Empagliflozin: a potential therapeutic approach for autophagy and Klotho modulation in Diabetic Kidney Disease
Marcella L Franco, Stephany Beyerstedt, Bruno S Barbosa, Tuany R Alves, Andrei F da Silva, Melise O Mariano, Alanah K Carlos, Jaqueline Arjona, Gleice R Josefi-Rocha, Rosana Maria Cardoso de Bastos¹, Érika B RangelAbstract
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.