Dysregulated microRNAs involved in contrast- induced acute kidney injury in rat and human
Dysregulated microRNAs involved in contrast- induced acute kidney injury in rat and human
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DOI：
10.3109/0886022x.2015.1077322
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发表时间：
2015-10-21
期刊：
影响因子：
3
通讯作者：
Gomez-Perez, F.
中科院分区：
文献类型：
--
作者：
Gutierrez-Escolano, A.;Santacruz-Vazquez, E.;Gomez-Perez, F.
背景资料：造影剂肾病（CIN）是一种复杂的急性肾病综合征，发生在血管内造影剂输注后，与不良心血管事件的风险增加相关。虽然没有理想的生物标志物用于早期诊断CIN，但我们假设特定循环microRNA（miRNA）物质的水平可能起这样的作用。方法：采用miRNA芯片技术检测CIN大鼠肾组织中的miRNA。进行实时PCR以验证微阵列测定的结果。在大鼠血浆中检测到的肾脏富集的miRNA用作筛选CIN的生物标志物。从CIN大鼠模型获得的结果在患有CIN的人类患者中得到进一步验证。结果如下：在CIN和对照组大鼠肾组织中有51个miRNAs表达异常，其中17个miRNAs在CIN大鼠肾组织中的表达变化大于非CIN对照组大鼠的2倍。在从肾组织中筛选出的17种异常表达的miRNAs中，只有6种在CIN大鼠血浆中也显示出显著不同的表达。与非CIN对照大鼠相比，CIN大鼠血浆中miR-30家族3个成员（miR-30 a、miR-30 c和miR-30 e）以及miR-320的水平显著升高，而miRNA let-7a和miR-200 a的血浆水平显著降低。在用人血浆样品进行的这些结果的验证研究中，当与非CIN患者相比时，仅miR-30 a、miR-30 c和miR-30 e在CIN患者中显示> 2倍的增加。为检查miR-30 a、miR-30 c和miR-30 e区分CIN患者与非CIN患者的能力而构建的受试者操作曲线显示AUC分别为0.954、0.888和0.835。结论：我们的研究提供了第一个证据表明，血浆miRNA，特别是三个miR-30家族成员（miR-30 a，miR-30 c和miR-30 e），可能作为CIN的早期生物标志物和（或）靶候选者。
Background: Contrast-induced nephropathy (CIN) is a complex syndrome of acute nephropathy that occurs following infusion of intravascular contrast agents, and is associated with an increased risk for adverse cardiovascular events. While there is no ideal biomarker for making an early diagnosis of CIN, we hypothesized that levels of specific circulating microRNA (miRNA) species might serve such a role. Methods: miRNA microarray assays were used to detect miRNAs in the kidney tissue of rats studied as an animal model of CIN. Real-time PCR was performed to validate results of the microarray assays. Kidney-enriched miRNAs detected in rat plasma were used as biomarkers to screen for CIN. Results obtained from the rat model of CIN were further validated in human patients with CIN. Results: Fifty-one miRNAs were aberrantly expressed in the kidney tissues between CIN and control rats; and among these, 17 miRNAs showed a >2-fold change of expression in the kidney tissues of CIN rats when compared with their expressions in non-CIN control rats. Among the 17 miRNAs aberrantly-expressed miRNAs screened from kidney tissue, only six also showed significantly different expression in the plasma of CIN rats. When compared with their levels in non-CIN control rats, the levels of three miR-30 family members (miR-30a, miR-30c, and miR-30e), as well as miR-320, were significantly increased in the plasma of CIN rats, while the plasma levels of miRNAs let-7a and miR-200a were significantly decreased. In a validation study of these results conducted with human plasma samples, only miR-30a, miR-30c, and miR-30e showed > 2-fold increases in CIN patients when compared with non-CIN patients. Receiver operating curves constructed to examine the abilities of miR-30a, miR-30c, and miR-30e to discriminate CIN patients from non-CIN patients showed AUCs of 0.954, 0.888, and 0.835, respectively. Conclusions: Our study provides the first evidence that plasma miRNAs, and especially three miR-30 family members (miR-30a, miR-30c, and miR-30e), might serve as early biomarkers and (or) target candidates for CIN.