Exosomes isolated from melatonin-stimulated mesenchymal stem cells improve kidney function by regulating inflammation and fibrosis in a chronic kidney disease mouse model

被引:44
作者
Yea, Ji-Hye [1 ]
Yoon, Yeo Min [1 ]
Lee, Jun Hee [2 ,3 ,4 ,5 ,6 ]
Yun, Chul Won [1 ]
Lee, Sang Hun [1 ,7 ,8 ,9 ]
机构
[1] Soonchunhyang Univ, Med Sci Res Inst, Seoul Hosp, Seoul, South Korea
[2] Dankook Univ, Inst Tissue Regenerat Engn, Cheonan, South Korea
[3] Dankook Univ, Dept Nanobiomed Sci, Cheonan, South Korea
[4] Dankook Univ, BK21 PLUS NBM Global Res Ctr Regenerat Med, Cheonan, South Korea
[5] Dankook Univ, Coll Dent, Dept Oral Anat, Cheonan, South Korea
[6] Dankook Univ, Cell & Matter Inst, Cheonan, South Korea
[7] Soonchunhyang Univ, Dept Biochem, Coll Med, Cheonan, South Korea
[8] Soonchunhyang Univ, Coll Med, Dept Biochem, BK21FOUR Project2, Cheonan, South Korea
[9] Stembio Ltd, Asan, South Korea
基金
新加坡国家研究基金会;
关键词
Chronic kidney disease; mesenchymal stem cell; exosome; inflammation; fibrosis; EXTRACELLULAR VESICLES; RENAL FIBROSIS; SURVIVAL; EXPRESSION; TARGETS; REPAIR;
D O I
10.1177/20417314211059624
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Chronic kidney disease (CKD) is defined as structural and functional abnormalities of the kidney due to inflammation and fibrosis. We investigated the therapeutic effects of exosomes secreted by melatonin-stimulated mesenchymal stem cells (Exocue) on the functional recovery of the kidney in a CKD mouse model. Exocue upregulated gene expression of micro RNAs (miRNAs) associated with anti-inflammatory and anti-fibrotic effects. Exocue-treated groups exhibited low tumor necrosis factor-alpha and transforming growth factor-beta levels in serum and fibrosis inhibition in kidney tissues mediated through regulation of cell apoptosis and proliferation of fibrosis-related cells. Exocue treatment decreased the gene expression of CKD progression-related miRNAs. Moreover, the CKD severity was alleviated in the Exocue group via upregulation of aquaporin 2 and 5 levels and reduction of blood urea nitrogen and creatinine, resulting in functional recovery of the kidney. In conclusion, Exocue could be a novel therapeutic agent for treating CKD by regulating inflammation and fibrosis.
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页数:13
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