Abstract

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.

Details

Title
Bone marrow mesenchymal stem cell-derived exosomal miR-21a-5p alleviates renal fibrosis by attenuating glycolysis by targeting PFKM
Author
Xu, Shihao 1 ; Cheuk, Yin Celeste 2 ; Jia, Yichen 1 ; Chen, Tian 2 ; Chen, Juntao 1 ; Luo, Yongsheng 1 ; Cao, Yirui 1 ; Guo, Jingjing 1 ; Dong, Lijun 3 ; Zhang, Yi 4   VIAFID ORCID Logo  ; Shi, Yi 4 ; Rong, Ruiming 5 

1  Fudan University, Department of Urology, Zhongshan Hospital, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443); Shanghai Key Laboratory of Organ Transplantation, Shanghai, China (GRID:grid.413087.9) (ISNI:0000 0004 1755 3939) 
2  Fudan University, Department of Urology, Huashan Hospital, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443) 
3  Tongji University, Operation Room, Shanghai Tenth People’s Hospital, Shanghai, China (GRID:grid.24516.34) (ISNI:0000000123704535) 
4  Shanghai Key Laboratory of Organ Transplantation, Shanghai, China (GRID:grid.413087.9) (ISNI:0000 0004 1755 3939); Fudan University, Institute of Clinical Science, Zhongshan Hospital, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443) 
5  Fudan University, Department of Urology, Zhongshan Hospital, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443); Shanghai Key Laboratory of Organ Transplantation, Shanghai, China (GRID:grid.413087.9) (ISNI:0000 0004 1755 3939); Fudan University, Department of Transfusion, Zhongshan Hospital, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443) 
Publication year
2022
Publication date
Oct 2022
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41419-022-05305-7
ProQuest document ID
2725463100
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.