MicroRNA-21 Attenuates Renal Ischemia Reperfusion Injury Via Targeting Caspase Signaling in Mice
MicroRNA-21 Attenuates Renal Ischemia Reperfusion Injury Via Targeting Caspase Signaling in Mice
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DOI：
10.1159/000368202
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发表时间：
2014-01-01
影响因子：
4.2
通讯作者：
Ye, Zhenfeng
中科院分区：
文献类型：
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作者：
Hu, Honglin;Jiang, Wei;Ye, Zhenfeng
背景资料：微小RNA（microRNAs，miR）作为肾缺血再灌注损伤（ischemic reperfusion injury，IRI）的基因表达调控因子和潜在的诊断工具已成为研究热点。本研究旨在探讨miR-21的分子调控和功能，并分析caspase和miR-21在实验性肾缺血再灌注模型中表达水平的关系。将雄性BALB/c小鼠随机分为以下组：pre-miR-21 + IRI组、Pre-miR-21 + IRI组、Pre-miR-21 + IRI组、PBS + IRI组、pre-miR-21+假手术组、Pre-miR-21+假手术组、PBS +假手术组。在诱导缺血前24和6小时腹膜内施用pre-miR-21或pre-miR-21（200 ng/kg体重）。结果：miR-21表达上调的小鼠血尿素氮（BUN）、肌酐水平降低，组织病理学评分降低，程序性细胞死亡4（PDCD 4）mRNA和活性caspase-3、caspase-8蛋白表达降低。miR-21通过抑制PDCD 4基因和活性caspase 3/8片段的表达而具有抗凋亡特性。miR-21在我们的肾IRI小鼠模型中发挥显著的功能保护作用。(C)2014 S. Karger AG，巴塞尔。
Background: MicroRNAs (miR) have come into focus as powerful regulators of gene expression and potential diagnostic tools during renal ischemia reperfusion injury (IRI). The aim of this study was to investigate the molecular regulation and function of miR-21, and to analyze the relationship between caspases and miR-21 expression levels in an experimental model of renal IRI.Methods: IRI was induced by bilateral renal ischemia for 45 min followed by reperfusion. The male BALB/c mice were randomly assigned to the following groups: pre-miR-21 + IRI group, antagomiR-21 + IRI group, PBS + IRI group, pre-miR-21 + sham operation group, antagomiR-21 + sham operation group, PBS + sham operation group. The pre-miR-21 or antagomiR-21 was administered intraperitoneally (200 ng/kg weight) 24 and 6 h before induction of ischemia. Renal function, histological damage, renal cell apoptosis proteins were evaluated at 24 h after reperfusion.Results: Mice upregulated miR-21 had lower plasma levels of blood urea nitrogen (BUN) and creatinine, lower histopathological scores and a decrease in programmed cell death 4 (PDCD4) mRNA and active caspase-3, caspase-8 proteins expressions.Conclusions: miR-21 is endowed with anti-apoptotic properties by suppressing the expression of PDCD4 gene and active caspase 3/8 fragments in the condition of renal IRI. miR-21 exerts significant functional protection in our renal murine model of IRI. (C) 2014 S. Karger AG, Basel.