Bone marrow mesenchymal stem cell-derived exosomal miR-21a-5p alleviates renal fibrosis by attenuating glycolysis by targeting PFKM

被引：33
|
作者：
Xu, Shihao [1 ,2 ]
Cheuk, Yin Celeste [3 ]
Jia, Yichen [1 ,2 ]
Chen, Tian [3 ]
Chen, Juntao [1 ,2 ]
Luo, Yongsheng [1 ,2 ]
Cao, Yirui [1 ,2 ]
Guo, Jingjing [1 ,2 ]
Dong, Lijun [4 ]
Zhang, Yi [2 ,5 ]
Shi, Yi [2 ,5 ]
Rong, Ruiming [1 ,2 ,6 ]
机构：
[1] Fudan Univ, Zhongshan Hosp, Dept Urol, Shanghai 200032, Peoples R China
[2] Shanghai Key Lab Organ Transplantat, Shanghai 200032, Peoples R China
[3] Fudan Univ, Huashan Hosp, Dept Urol, Shanghai 200040, Peoples R China
[4] Tongji Univ, Shanghai Peoples Hosp 10, Operat Room, Shanghai 200072, Peoples R China
[5] Fudan Univ, Zhongshan Hosp, Inst Clin Sci, Shanghai 200032, Peoples R China
[6] Fudan Univ, Zhongshan Hosp, Dept Transfus, Shanghai 200032, Peoples R China
来源：
CELL DEATH & DISEASE | 2022年 / 13卷 / 10期
基金：
国家重点研发计划; 上海市自然科学基金; 中国国家自然科学基金;
关键词：
TUBULAR EPITHELIAL-CELLS; KIDNEY; ACTIVATION; PROTECT;
D O I：
10.1038/s41419-022-05305-7
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Renal fibrosis is a common pathological feature and outcome of almost all chronic kidney diseases, and it is characterized by metabolic reprogramming toward aerobic glycolysis. Mesenchymal stem cell-derived exosomes (MSC-Exos) have been proposed as a promising therapeutic approach for renal fibrosis. In this study, we investigated the effect of MSC-Exos on glycolysis and the underlying mechanisms. We demonstrated that MSC-Exos significantly ameliorated unilateral ureter obstruction (UUO)-induced renal fibrosis by inhibiting glycolysis in tubular epithelial cells (TECs). miRNA sequencing showed that miR-21a-5p was highly enriched in MSC-Exos. Mechanistically, miR-21a-5p repressed the expression of phosphofructokinase muscle isoform (PFKM), a rate-limiting enzyme of glycolysis, thereby attenuating glycolysis in TECs. Additionally, knockdown of miR-21a-5p abolished the renoprotective effect of MSC-Exos. These findings revealed a novel role for MSC-Exos in the suppression of glycolysis, providing a new insight into the treatment of renal fibrosis.
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页数：10
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