期刊
EUROPEAN JOURNAL OF MEDICAL RESEARCH
卷 27, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s40001-022-00742-8
关键词
BMSC-derived exosome; Renoprotective; Klotho; 5; 6 Nephrectomy rats
资金
- Natural Science Foundation of Zhejiang Province [Y20H050004, LQ21H290005]
- Public Welfare Technology Application Research Program of Zhejiang Province [LGC21H290002]
This study investigated 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). The results showed that transplantation of rBMSC-derived exosomes reduced urinary protein excretion, serum creatinine (SCr), and blood urea nitrogen (BUN) levels in CKD rats. Renal pathology was also improved in the exosome-treated rats. Mechanistically, the exosomes upregulated the activity and expression of klotho. These findings provide a theoretical basis for the application of rBMSC-derived exosomes in CKD therapy.
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.
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