MiR-21 is required for efficient kidney regeneration in fish.
MiR-21 is required for efficient kidney regeneration in fish.
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DOI：
10.1186/s12861-015-0089-2
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发表时间：
2015-11-17
影响因子：
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通讯作者：
Englert C
中科院分区：
文献类型：
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作者：
Hoppe B;Pietsch S;Franke M;Engel S;Groth M;Platzer M;Englert C
由心血管疾病或使用具有肾毒性副作用的抗生素引起的哺乳动物急性肾损伤是一种危及生命的疾病，因为肾单位的损失在哺乳动物中是不可逆的。相比之下，鱼类即使在成年期也能够产生新的肾单位，从而为研究肾小管再生提供了良好的模型。在这里，我们使用短命的鳉鱼 Nothobranchius Furzeri 研究了庆大霉素诱导的肾损伤后的早期反应。一组 microRNA 在肾损伤后出现差异表达，其中 miR-21 表达上调。锁核酸修饰的抗miR-21有效地降低了miR-21活性，并导致增殖反应滞后、细胞凋亡增强和再生总体延迟。转录组分析发现细胞凋亡是一个受到 antimiR-21 给药显着影响的过程。结合功能数据，这表明 miR-21 在鱼类肾脏再生过程中充当促增殖和抗凋亡因子。介导其对增殖和凋亡影响的可能下游候选基因包括 igfbp3 和 fosl1 等基因。总之，我们的研究结果扩展了 miR-21 在肾脏中的作用。我们首次展示其在再生中的功能参与，表明快速增殖和减少细胞凋亡对于有效的肾小管再生很重要。本文的在线版本 (doi:10.1186/s12861-015-0089-2) 包含补充材料，可供授权用户使用。
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. 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. 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. The online version of this article (doi:10.1186/s12861-015-0089-2) contains supplementary material, which is available to authorized users.