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下调 miR-574-5p 抑制 HK-2 细胞活力,并预测脓毒症患者急性肾损伤的发生。

Downregulation of miR-574-5p inhibits HK-2 cell viability and predicts the onset of acute kidney injury in sepsis patients.

机构信息

Emergent Intensive Care Unit, Shengli Oilfield Central Hospital, Dongying, China.

Department of Critical Care Medicine, Shengli Oilfield Central Hospital, Dongying, China.

出版信息

Ren Fail. 2021 Dec;43(1):942-948. doi: 10.1080/0886022X.2021.1939051.

Abstract

BACKGROUND

Increased levels of microRNA-574-5p (miR-574-5p) have been found to be associated with increased survival of septic patients, indicating the potential role of miR-574-5p in protecting against septic progression and complications. Acute kidney injury (AKI) is one of the most common and serious complications of sepsis. Therefore, the aim of this study was to test these hypotheses: (1) in a renal cell culture line (HK-2), upregulated expression of miR-574-5p increases, and downregulated expression of miR-574-5p decreases cell viability, and (2) serum levels of miR-574-5p from patients with sepsis and AKI are lower than those of patients with sepsis but no AKI.

METHODS

The expression of miR-574-5p was regulated by cell transfection in HK-2 cells, and HK-2 cell viability was measured using the Cell Counting Kit-8. Serum miR-574-5p expression was analyzed using qRT-PCR. The predictive value of miR-574-5p for AKI onset was evaluated using the receiver operating characteristic curve and logistic regression analysis.

RESULTS

The overexpression of miR-574-5p promoted HK-2 cell viability. Fifty-eight sepsis patients developed AKI, who had significantly lower miR-574-5p expression. miR-574-5p expression was decreased with AKI stage increase and correlated with kidney injury biomarker and had relatively high accuracy to predict AKI occurrence from sepsis patients.

CONCLUSION

Overexpression of miR-574-5p in cultured HK-2 cells increases cell viability and knocked-down expression of miR-574-5p decreases cell viability. Consistently, septic patients with AKI were found to have less upregulation of miR-574-5p expression compared to septic patients without AKI. Thus, serum miR-574-5p may provide a novel biomarker for septic AKI.

摘要

背景

研究发现,miR-574-5p(微小 RNA-574-5p)水平升高与脓毒症患者生存率升高有关,表明 miR-574-5p 在防止脓毒症进展和并发症方面具有潜在作用。急性肾损伤(AKI)是脓毒症最常见和最严重的并发症之一。因此,本研究旨在检验以下假设:(1)在肾细胞培养系(HK-2)中,上调 miR-574-5p 的表达可增加细胞活力,下调 miR-574-5p 的表达可降低细胞活力;(2)脓毒症合并 AKI 患者的血清 miR-574-5p 水平低于脓毒症但无 AKI 患者。

方法

通过细胞转染调节 HK-2 细胞中 miR-574-5p 的表达,用细胞计数试剂盒-8 测定 HK-2 细胞活力。采用 qRT-PCR 分析血清 miR-574-5p 表达。采用受试者工作特征曲线和逻辑回归分析评估 miR-574-5p 对 AKI 发病的预测价值。

结果

miR-574-5p 的过表达促进了 HK-2 细胞的活力。58 例脓毒症患者发生 AKI,其 miR-574-5p 表达显著降低。miR-574-5p 的表达随着 AKI 分期的增加而降低,与肾损伤生物标志物相关,对脓毒症患者发生 AKI 的预测具有较高的准确性。

结论

在培养的 HK-2 细胞中过表达 miR-574-5p 可增加细胞活力,敲低 miR-574-5p 的表达可降低细胞活力。同样,与无 AKI 的脓毒症患者相比,脓毒症合并 AKI 患者的 miR-574-5p 表达上调程度较低。因此,血清 miR-574-5p 可能为脓毒症 AKI 提供一种新的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a11f/8901276/b3a4664cff87/IRNF_A_1939051_F0001_B.jpg

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