BMSC-derived exosomes protect against kidney injury through regulating klotho in 5/6 nephrectomy rats

Abstract

Aim: The aim of this study was to investigate the renoprotective effects of exosomes derived from rat bone marrow mesenchymal stem cells (rBMSCs) in a rat model of 5/6 nephrectomy (Nx)-induced chronic kidney disease (CKD). Methods: A rat model of 5/6 Nx-induced CKD was established using conventional method. rBMSC-derived exosomes were isolated using ultracentrifugation and characterized. The exosomes were injected into 5/6 Nx rats through the caudal vein. After 12 weeks, 24 h proteinuria, serum creatinine (SCr), and blood urea nitrogen (BUN) levels were evaluated, and renal pathology was analyzed by H&E and Masson staining, and transmission electron microscopy. The expression of klotho was analyzed and the activity of the klotho promoter was evaluated using a luciferase reporter assay. Results: The isolated exosomes showed typical morphological features. Exosomes transplantation reduced 24 h urinary protein excretion, and SCr and BUN levels in 5/6 Nx-induced CKD rats. Furthermore, renal pathology was improved in the exosome-treated 5/6 Nx rats. Mechanistically, the exosomes significantly upregulated the activity of klotho promoter and its expression. Conclusions: Transplantation of rBMSC-derived exosomes may protect against kidney injury, probably by regulating klotho activity and expression. Our results provide a theoretical basis for the application of rBMSC-derived exosomes in CKD therapy.