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

Cell Death Dis. 2022 Oct 17;13(10):876. doi: 10.1038/s41419-022-05305-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Exosomes* / genetics
  • Exosomes* / metabolism
  • Fibrosis
  • Glycolysis / genetics
  • Humans
  • Kidney Diseases* / metabolism
  • Mesenchymal Stem Cells* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Muscles / metabolism
  • Phosphofructokinase-1, Muscle Type* / genetics
  • Phosphofructokinase-1, Muscle Type* / metabolism
  • Protein Isoforms / metabolism

Substances

  • MicroRNAs
  • PFKM protein, human
  • Phosphofructokinase-1, Muscle Type
  • Protein Isoforms
  • MIRN21 microRNA, human