MicroRNA-206 and its down-regulation of Wilms'Tumor-1 dictate podocyte health in adriamycin-induced nephropathy

Ren Fail. 2016 Jul;38(6):989-95. doi: 10.3109/0886022X.2016.1165119. Epub 2016 Apr 8.


Background: Focal segmental glomerulosclerosis (FSGS) is a frequent and severe glomerular disease characterized by destabilization of podocyte foot processes. Emerging evidence suggests that microRNAs play crucial roles in podocyte homeostasis. The aim of the present study was to determine the role of miR-206 in podocyte injury and to elucidate the mechanisms responsible for the damage to podocyte.

Methods: FSGS nephropathy model was induced by a single intravenous injection of Adriamycin (ADR) in BALB/c mice and the levels of proteinuria were measured on week of 1,3,5. The conditionally immortalized mouse podocyte cell line 5 was either transfected with microRNA mimics or negative control. Real-time PCR analysis was conducted to demonstrate the microRNA level in the glomeruli. Expression of Wilms' tumor-1 (WT1) and synaptopodin were detected by immunofluorescence and western blotting.

Results: The results revealed that miR-206 was up-regulated in ADR nephropathy mice, which led to severe podocyte injury and inhibited the expression of WT1 and synaptopodin. Using luciferase reporter assays, WT1 was identified as a target gene of miR-206. In vitro, over expression of miR-206 induced WT1 and synaptopodin degradation and actin rearrangement, initiating a catastrophic collapse of the entire podocyte-stabilizing system.

Conclusions: Over expression of miR-206 promotes podocyte injury via downregulation of WT1, which provides a new pathogenic mechanism for FSGS and miR-206 may be a potential therapeutic target.

Keywords: Actin; Focal segmental glomerulosclerosis; WT1; microRNA-206; podocyte.

MeSH terms

  • Animals
  • Cell Line
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Doxorubicin / adverse effects*
  • Glomerulosclerosis, Focal Segmental / chemically induced
  • Glomerulosclerosis, Focal Segmental / genetics*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • Microfilament Proteins / genetics*
  • Microscopy, Electron
  • Podocytes / pathology*
  • Podocytes / ultrastructure
  • Proteinuria
  • Repressor Proteins / genetics*
  • Up-Regulation / drug effects
  • WT1 Proteins


  • MicroRNAs
  • Microfilament Proteins
  • Mirn206 microRNA, mouse
  • Repressor Proteins
  • Synpo protein, mouse
  • WT1 Proteins
  • WT1 protein, mouse
  • Doxorubicin