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

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 m...

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Published inEuropean journal of medical research Vol. 27; no. 1; pp. 1 - 118
Main Authors Wan, Feng, Yang, Ru-chun, Tang, Yue-wen, Tang, Xuan-li, Ye, Tian, Zheng, Jie, Zhang, Hua-qin, Lin, Yi
Format Journal Article
LanguageEnglish
Published London BioMed Central Ltd 11.07.2022
BioMed Central
BMC
Subjects
5/6 Nephrectomy rats
Biosynthesis
BMSC-derived exosome
Bone marrow
Chronic kidney failure
Kidneys
Klotho
Medical research
Renoprotective
Rodents
Stem cells
Urea
Variance analysis
Japan
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Summary: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. Keywords: BMSC-derived exosome, Renoprotective, Klotho, 5/6 Nephrectomy rats
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ISSN:2047-783X
0949-2321
2047-783X
DOI:10.1186/s40001-022-00742-8