MiR-21 is required for efficient kidney regeneration in fish

BMC Dev Biol. 2015 Nov 17;15:43. doi: 10.1186/s12861-015-0089-2.

Abstract

Background: Acute kidney injury in mammals, which is caused by cardiovascular diseases or the administration of antibiotics with nephrotoxic side-effects is a life-threatening disease, since loss of nephrons is irreversible in mammals. In contrast, fish are able to generate new nephrons even in adulthood and thus provide a good model to study renal tubular regeneration.

Results: Here, we investigated the early response after gentamicin-induced renal injury, using the short-lived killifish Nothobranchius furzeri. A set of microRNAs was differentially expressed after renal damage, among them miR-21, which was up-regulated. A locked nucleic acid-modified antimiR-21 efficiently knocked down miR-21 activity and caused a lag in the proliferative response, enhanced apoptosis and an overall delay in regeneration. Transcriptome profiling identified apoptosis as a process that was significantly affected upon antimiR-21 administration. Together with functional data this suggests that miR-21 acts as a pro-proliferative and anti-apoptotic factor in the context of kidney regeneration in fish. Possible downstream candidate genes that mediate its effect on proliferation and apoptosis include igfbp3 and fosl1, among other genes.

Conclusion: In summary, our findings extend the role of miR-21 in the kidney. For the first time we show its functional involvement in regeneration indicating that fast proliferation and reduced apoptosis are important for efficient renal tubular regeneration.

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / therapy
  • Animals
  • Apoptosis / genetics
  • Cell Proliferation / genetics
  • Cyprinodontiformes / genetics*
  • Gene Expression Regulation, Developmental / genetics*
  • Gentamicins
  • Kidney Tubules / growth & development*
  • Kidney Tubules / metabolism
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • Regeneration / genetics*
  • Regeneration / physiology

Substances

  • Gentamicins
  • MicroRNAs