微小RNA-30c通过抑制NLRP3炎性小体减轻造影剂诱导的急性肾损伤。
MicroRNA-30c attenuates contrast-induced acute kidney injury by suppressing NLRP3 inflammasome.
作者信息
Xu Jun, Ma Liang, Fu Ping
机构信息
Division of Nephrology and National Clinical Research Center for Geriatrics, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu 610041, China; Division of Nephrology, The Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang 550014,China.
Division of Nephrology and National Clinical Research Center for Geriatrics, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu 610041, China.
出版信息
Int Immunopharmacol. 2020 Oct;87:106457. doi: 10.1016/j.intimp.2020.106457. Epub 2020 Jul 16.
BACKGROUNDS
Contrast-induced acute kidney injury (CIAKI) is the third most common cause of hospital-acquired AKI. It has been demonstrated that microRNA-30c (miR-30c) was upregulated in the CIAKI. However, the underlying mechanism remain unclear.
METHODS
The CIAKI was induced in miniature pig. The expression profile of miR-30c in the kidney was evaluated by qPCR. The pathways regulated by miR-30c was identified by qPCR and western blot on renal tubular epithelial cells isolated from miniature pig. Finally, the potential therapeutic application of targeting miR-30c was assessed in the pig model of CIAKI.
RESULTS
The miR-30c was up-regulated in miniature pig with CIAKI. The miR-30c suppressed cell apoptosis, expression of NLRP3, the secretion of IL-1β and caspase-1 p10 on renal cells stimulated by iohexol in vitro. In the pig model, miR-30c inhibited the CIAKI development.
CONCLUSION
Our data demonstrated that the miR-30c induced by CIAKI could suppress cell apoptosis and kidney injury via targeting NLRP3. Therefore, targeting miR-30c might be a novel therapeutic candidate for CIAKI treatment and prevention.
背景
对比剂诱导的急性肾损伤（CIAKI）是医院获得性急性肾损伤的第三大常见原因。已有研究表明，微小RNA-30c（miR-30c）在CIAKI中表达上调。然而，其潜在机制仍不清楚。
方法
在小型猪中诱导CIAKI。通过qPCR评估肾脏中miR-30c的表达谱。通过对从小型猪分离的肾小管上皮细胞进行qPCR和蛋白质印迹法，确定受miR-30c调控的信号通路。最后，在CIAKI猪模型中评估靶向miR-30c的潜在治疗应用。
结果
CIAKI小型猪中miR-30c上调。在体外，miR-30c抑制了碘海醇刺激的肾细胞的细胞凋亡、NLRP3的表达、IL-1β的分泌和caspase-1 p10。在猪模型中，miR-30c抑制了CIAKI的发展。
结论
我们的数据表明，CIAKI诱导的miR-30c可通过靶向NLRP3抑制细胞凋亡和肾损伤。因此，靶向miR-30c可能是治疗和预防CIAKI的新型候选疗法。
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