Cell Death and Disease (Oct 2022)

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

  • Shihao Xu,
  • Yin Celeste Cheuk,
  • Yichen Jia,
  • Tian Chen,
  • Juntao Chen,
  • Yongsheng Luo,
  • Yirui Cao,
  • Jingjing Guo,
  • Lijun Dong,
  • Yi Zhang,
  • Yi Shi,
  • Ruiming Rong

DOI
https://doi.org/10.1038/s41419-022-05305-7
Journal volume & issue
Vol. 13, no. 10
pp. 1 – 10

Abstract

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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.