Exosomes from adipose-derived mesenchymal stem cells ameliorate bladder dysfunction in diabetic rats by attenuating oxidative stress via the PTEN/PI3K/AKT/GSK-3β signaling pathway

Abstract Diabetic bladder dysfunction (DBD) is a common urinary system complication in diabetic patients, with oxidative stress (OS) being a key factor in its onset and progression. Adipose-derived stem cell exosomes (ADSC-exos) hold potential for treating OS-related diseases. In this study, we established high glucose-induced cell models and diabetic rat models to investigate the role and molecular mechanisms of ADSC-exos in mitigating OS in DBD. The results demonstrated that ADSC-exos inhibited intracellular ROS generation, downregulated PTEN expression, activated the PI3K/AKT pathway, promoted GSK-3β degradation, reversed NRF2 suppression, and enhanced the expression of downstream antioxidant proteins. In diabetic rats, ADSC-exos improved bladder function by reducing maximum voiding pressure, prolonging voiding intervals, and decreasing bladder tissue fibrosis and apoptosis. Further analysis revealed that miRNA-21-5p is highly enriched in ADSC-exos. Bioinformatics predictions identify PTEN as a target of miRNA-21-5p. Overexpression of miRNA-21-5p reversed PTEN-mediated suppression of the antioxidant stress system. In summary, ADSC-exos alleviate OS and improve bladder function in diabetic rats via the PTEN/PI3K/AKT/GSK-3β signaling pathway, in which miRNA-21-5p may play a certain role.