MiR-21 is required for efficient kidney regeneration in fish

Abstract

BackgroundAcute 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.ResultsHere, 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.ConclusionIn 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12861-015-0089-2) contains supplementary material, which is available to authorized users.

Histomicroscopy and normal anatomy of the adult killifish Aphanius hormuzensis (Teleostei; Aphaniidae) from the Persian Gulf coastal environment

“…Among the studied organs in A. hormuzensis , the kidney, liver and gas bladder (or swim bladder) were somewhat similar to the condition seen in other killifishes. The anatomical position and structure of the kidney (Figure a) is almost similar to the kidney of the short‐lived killifish N. furzeri (Cyprinodontiformes, Nothobranchiidae) (Hoppe et al, ; Figure b) and also to the kidney of the Japanese medaka, O. latipes (Fedorova et al, ; Figure ). As seen in A. hormuzensis , N. furzeri and O. latipes have an elongated kidney with clear head and tail portions.…”

“…As seen in A. hormuzensis , N. furzeri and O. latipes have an elongated kidney with clear head and tail portions. The kidney in D. rerio , is similar to the above mentioned species with respect to the location of the kidney at the dorsal side of the body, but differs because its kidney showed three distinct parts from anterior to posterior including head, trunk and tail (Hoppe et al, ; Figure a).…”

The African turquoise killifish: A research organism to study vertebrate aging and diapause

“…For example, the turquoise killifish, with a short lifespan and ability to regenerate tissues, is in a great position to study the interplay between tissue regeneration and aging in vertebrates (Hoppe et al., 2015; Wendler et al., 2015). …”

MicroRNA-133b Negatively Regulates Zebrafish Single Mauthner-Cell Axon Regeneration through Targeting tppp3 in Vivo

“…To further verify the specific role of miR-133b in regulating axon regeneration, we overexpressed another two miRNAs, miR-23a and miR-21, with the same assay as mentioned above. Together with qRT-PCR results confirming that miR-23a and miR-21 were indeed overexpressed in zebrafish via vector-based miRNA expression assay (Figure 1C ), we found out that miR-23a, a miRNA that has not been reported to be associated with axon regeneration, had no obvious effect on M-cell axon regeneration; while miR-21, which has been shown to promote regeneration in different organs (Strickland et al, 2011 ; Han et al, 2014 ; Hoppe et al, 2015 ), remarkably promoted M-cell axon regeneration (control: 243.7 ± 32.9 μm, n = 33 fish vs. miR-23a OE: 229.0 ± 62.4 μm, n = 10 fish vs. miR-21 OE: 778.4 ± 60.8 μm, n = 12 fish; Figures 1E,F ).…”