title: MiR-21 is required for efficient kidney regeneration in fish.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Molecular Genetics Laboratory, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, 07745, Jena, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Hoppe
authors.affiliation: Molecular Genetics Laboratory, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, 07745, Jena, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Pietsch
authors.affiliation: Molecular Genetics Laboratory, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, 07745, Jena, Germany.|Present address: Research Group of Development & Disease, Max Planck Institute for Molecular Genetics, 14195, Berlin, Germany.|Institute for Medical and Human Genetics, Charité Universitätsmedizin Berlin, 13353, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Franke
authors.affiliation: Molecular Genetics Laboratory, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, 07745, Jena, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Engel
authors.affiliation: Genome Analysis, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, 07745, Jena, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Groth
authors.affiliation: Genome Analysis, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, 07745, Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Platzer
authors.affiliation: Molecular Genetics Laboratory, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, 07745, Jena, Germany. cenglert@fli-leibniz.de.|Faculty of Biology and Pharmacy, Friedrich Schiller University of Jena, Fürstengraben 1, 07743, Jena, Germany. cenglert@fli-leibniz.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Englert
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000628:therapy; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D003532:Cyprinodontiformes / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D005839:Gentamicins; D007684:Kidney Tubules / Q000254:growth & development* / Q000378:metabolism; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D012038:Regeneration / Q000235:genetics* / Q000502:physiology
chemical_list: D005839:Gentamicins; D035683:MicroRNAs