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

MiR-21 is required for efficient kidney regeneration in fish.

Author information

1
Molecular Genetics Laboratory, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, 07745, Jena, Germany.
2
Present address: Research Group of Development & Disease, Max Planck Institute for Molecular Genetics, 14195, Berlin, Germany.
3
Institute for Medical and Human Genetics, Charité Universitätsmedizin Berlin, 13353, Berlin, Germany.
4
Genome Analysis, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, 07745, Jena, Germany.
5
Molecular Genetics Laboratory, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, 07745, Jena, Germany. cenglert@fli-leibniz.de.
6
Faculty of Biology and Pharmacy, Friedrich Schiller University of Jena, Fürstengraben 1, 07743, Jena, Germany. cenglert@fli-leibniz.de.

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.

PMID:
26577279
PMCID:
PMC4650918
DOI:
10.1186/s12861-015-0089-2
[Indexed for MEDLINE]
Free PMC Article

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