MiR-21 is required for efficient kidney regeneration in fish

BMC Developmental Biology

Christoph Englert²  Matthias Platzer³  Marco Groth³  Sven Engel¹  Martin Franke⁴  Stefan Pietsch¹  Beate Hoppe¹ 

[1] Molecular Genetics Laboratory, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, Jena, 07745, Germany;Faculty of Biology and Pharmacy, Friedrich Schiller University of Jena, Fürstengraben 1, Jena, 07743, Germany;Genome Analysis, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, Jena, 07745, Germany;Institute for Medical and Human Genetics, Charité Universitätsmedizin Berlin, Berlin, 13353, Germany

关键词: fosl1;    igfbp3;    Teleost killifish;    miRNA;    LNA;    Kidney regeneration;   

Others  :  1234326
DOI  :  10.1186/s12861-015-0089-2

 received in 2015-06-16, accepted in 2015-10-25,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Hoppe et al.

【 图 表 】

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