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

Autor: Xu S; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.; Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China., Cheuk YC; Department of Urology, Huashan Hospital, Fudan University, Shanghai, 200040, China., Jia Y; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.; Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China., Chen T; Department of Urology, Huashan Hospital, Fudan University, Shanghai, 200040, China., Chen J; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.; Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China., Luo Y; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.; Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China., Cao Y; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.; Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China., Guo J; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.; Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China., Dong L; Operation Room, Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200072, China., Zhang Y; Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China. yzhang_med@fudan.edu.cn.; Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. yzhang_med@fudan.edu.cn., Shi Y; Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China. shi.yi@zs-hospital.sh.cn.; Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. shi.yi@zs-hospital.sh.cn., Rong R; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. rong.ruiming@zs-hospital.sh.cn.; Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China. rong.ruiming@zs-hospital.sh.cn.; Department of Transfusion, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. rong.ruiming@zs-hospital.sh.cn.
Jazyk: angličtina
Zdroj: Cell death & disease [Cell Death Dis] 2022 Oct 17; Vol. 13 (10), pp. 876. Date of Electronic Publication: 2022 Oct 17.
DOI: 10.1038/s41419-022-05305-7
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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