Survival Motor Neuron (SMN) Protein Insufficiency Exacerbates Renal Ischemia/Reperfusion Injury
Survival Motor Neuron (SMN) Protein Insufficiency Exacerbates Renal Ischemia/Reperfusion Injury
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运动神经元存活 (SMN) 蛋白不足会加剧肾缺血/再灌注损伤
DOI：
10.3389/fphys.2019.00559
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发表时间：
2019-05-14
影响因子：
4
通讯作者：
Yao, Lei
中科院分区：
文献类型：
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作者：
Qian, Xiaoqian;Du, Yichao;Yao, Lei
运动神经元(SMN)蛋白的存活广泛参与剪接体的组装和核糖核蛋白的生物发生。SMN蛋白在肾脏中表达，可影响细胞死亡过程。然而，SMN在急性肾损伤(AKI)中的作用尚不清楚。在目前的研究中，我们发现在临床缺血性AKI和小鼠肾脏缺血再灌注损伤(IRI)模型中，SMN在肾脏中的表达都显著减少。然后，我们使用SMN杂合基因敲除(SMN+/-)小鼠，发现实验性IRI后，SMN+/-小鼠的肾功能、肾小管损伤和肾小管细胞凋亡的下降明显比它们的野生型小鼠严重。同时，在缺血SMN+/-小鼠中，核转录因子-kappab(NFkappa B)信号转导增强。在体外，二氯化钴(CoCl2)处理降低了近端肾小管上皮细胞SMN的表达。另外，瞬时转染针对SMN的小干扰RNA(SiRNA)可增强CoCl2诱导的细胞凋亡和激活NFkB信号通路，而瞬时转染全长SMN则可减弱其诱导的细胞凋亡和激活NFkB信号通路。综上所述，这项研究首次支持了SMN在缺血性AKI中的保护作用。
The survival of motor neuron (SMN) protein is ubiquitously involved in spliceosome assembly and ribonucleoprotein biogenesis. SMN protein is expressed in kidney and can affect cell death processes. However, the role of SMN in acute kidney injury (AKI) is largely unknown. In the current study, we found that the expression of SMN in the kidney was significantly reduced in both clinical ischemic AKI and a mouse model of renal ischemia-reperfusion injury (IRI). We then used SMN heterozygous knockout (SMN+/-) mice and found that the declines in renal function, tubular injury, and tubular cell apoptosis after experimental IRI were significantly more severe in SMN+/- mice than those in their wild-type littermates. Concomitantly, the canonical transcription factor nuclear factor-kappa b (NF kappa b) signaling was enhanced in ischemic SMN+/- mice. In vitro, cobalt dichloride (CoCl2) treatment reduced SMN expression in proximal tubular epithelial cells. In addition, CoCl2-induced apoptosis and activation of NFKb signaling pathway were enhanced by transient transfection of a small-interfering RNA (siRNA) against SMN while attenuated by transient transfection of a full-length SMN plasmid. Taken together, this study for the first time supported the protective role of SMN in ischemic AKI.