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血浆衍生的外泌体 hsa-miR-184 和 hsa-mir-6766-3p 作为儿童心脏手术相关急性肾损伤早期检测的有前途的诊断生物标志物。

Plasma-derived exosomal hsa-miR-184 and hsa-mir-6766-3p as promising diagnostic biomarkers for early detection of children's cardiac surgery-associated acute kidney injury.

机构信息

Department of Urology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

School of Basic Medical Sciences, Weifang Medical University, Weifang, China.

出版信息

Sci Rep. 2024 Sep 27;14(1):22387. doi: 10.1038/s41598-024-72737-w.

DOI:10.1038/s41598-024-72737-w
PMID:39333590
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11436921/
Abstract

There is little known about the contribution of exosomal microRNAs (exomiRs) in the children's cardiac surgery-associated acute kidney injury (CSA-AKI). This study aimed to find diagnostic biomarkers for predicting CSA-AKI in children. A prospective observational study was conducted from April 2020 to March 2021.According to the changes of serum creatinine (SCr) value and urine volume within 48 h, the children were divided into acute kidney injury (AKI) group and non-AKI group. Serum samples were collected 4 h after cardiac surgery. Isolation of extracellular vesicles (EVs) and extraction of exomiRs from serum samples. Illumina high-throughput sequencing was used to quantify exomiRs and screen candidate microRNAs (miRNAs). Expression levels of candidate miRNAs were validated using droplet digital polymerase chain reaction (ddPCR). Normal and injuried rats' kidney tissue were collected for tissue validation. In the pre-experimental stage (4 AKI vs. 4 non-AKI), hsa-miR-184, hsa-miR-4800-3p, hsa-miR-203a-3p and hsa-miR-6766-3p were selected as candidate genes. In the verification stage (8 AKI vs. 12 non-AKI), the expression of hsa-miR-184 in AKI group was significantly lower than that in non-AKI group (P = 0.031), and the expression of hsa-miR-4800-3p and hsa-miR-6766-3p in AKI group was significantly higher than that in non-AKI group (P = 0.01 and P = 0.047). There was no significant difference in the expression of hsa-miR-203a-3p between the two groups (P > 0.05). The expression of rats' kidney tissue rno-miR-184 in AKI group was significantly lower than that in the normal group (P = 0.044). The area under the curve (AUC) of AKI predicted by hsa-miR-184 is 0.7865 and the AUC of hsa-miR-6766-3p is 0.7708. Combined with two kinds of miRNAs, the area under the curve of AKI is predicted to be 0.8646. The change of exomiRs level in circulatory system occurred in the early stage after cardiac operation, and the changes of hsa-miR-184 and hsa-miR-6766-3p content in circulatory system could predict CSA-AKI well.

摘要

关于外泌体 microRNAs（exomiRs）在儿童心脏手术相关急性肾损伤（CSA-AKI）中的作用知之甚少。本研究旨在寻找预测儿童 CSA-AKI 的诊断生物标志物。一项前瞻性观察研究于 2020 年 4 月至 2021 年 3 月进行。根据术后 48 小时内血清肌酐（SCr）值和尿量的变化，将患儿分为急性肾损伤（AKI）组和非 AKI 组。术后 4 小时采集血清样本。分离细胞外囊泡（EVs）并从血清样本中提取 exomiRs。采用 Illumina 高通量测序定量 exomiRs，筛选候选 microRNAs（miRNAs）。采用液滴数字聚合酶链反应（ddPCR）验证候选 miRNA 的表达水平。收集正常和损伤大鼠肾组织进行组织验证。在预实验阶段（4 例 AKI 与 4 例非 AKI），选择 hsa-miR-184、hsa-miR-4800-3p、hsa-miR-203a-3p 和 hsa-miR-6766-3p 作为候选基因。在验证阶段（8 例 AKI 与 12 例非 AKI），AKI 组 hsa-miR-184 的表达明显低于非 AKI 组（P=0.031），AKI 组 hsa-miR-4800-3p 和 hsa-miR-6766-3p 的表达明显高于非 AKI 组（P=0.01 和 P=0.047）。两组间 hsa-miR-203a-3p 的表达无显著差异（P＞0.05）。AKI 组大鼠肾组织 rno-miR-184 的表达明显低于正常组（P=0.044）。hsa-miR-184 预测 AKI 的曲线下面积（AUC）为 0.7865，hsa-miR-6766-3p 的 AUC 为 0.7708。两种 miRNA 联合后，AKI 的 AUC 预测值为 0.8646。心脏手术后早期发生循环系统外泌体水平变化，循环系统中 hsa-miR-184 和 hsa-miR-6766-3p 含量的变化可较好地预测 CSA-AKI。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/026a/11436921/2551d06744ac/41598_2024_72737_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/026a/11436921/78dcd95622ef/41598_2024_72737_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/026a/11436921/4e88e6f65179/41598_2024_72737_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/026a/11436921/f6be5285921e/41598_2024_72737_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/026a/11436921/f2216bd21d4d/41598_2024_72737_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/026a/11436921/ad6c6a04d3ab/41598_2024_72737_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/026a/11436921/2551d06744ac/41598_2024_72737_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/026a/11436921/78dcd95622ef/41598_2024_72737_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/026a/11436921/4e88e6f65179/41598_2024_72737_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/026a/11436921/f6be5285921e/41598_2024_72737_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/026a/11436921/f2216bd21d4d/41598_2024_72737_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/026a/11436921/ad6c6a04d3ab/41598_2024_72737_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/026a/11436921/2551d06744ac/41598_2024_72737_Fig6_HTML.jpg

相似文献

[1]
Plasma-derived exosomal hsa-miR-184 and hsa-mir-6766-3p as promising diagnostic biomarkers for early detection of children's cardiac surgery-associated acute kidney injury.

Sci Rep. 2024-9-27

[2]
A Pilot Study Identifying a Set of microRNAs As Precise Diagnostic Biomarkers of Acute Kidney Injury.

PLoS One. 2015-6-16

[3]
Plasma microRNA-21 for the early prediction of acute kidney injury in patients undergoing major cardiac surgery.

Nephrol Dial Transplant. 2016-3-2

[4]
Early detection of cardiac surgery‑associated acute kidney injury by microRNA-21.

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[5]
Implications of dynamic changes in miR-192 expression in ischemic acute kidney injury.

Int Urol Nephrol. 2017-3

[6]
[Value of serum level of microRNA-494 in predicting prognosis of acute renal injury after cardiac surgery in children].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2019-12

[7]
[Value of serum miR-21-3p in predicting acute kidney injury in children with sepsis].

Zhongguo Dang Dai Er Ke Za Zhi. 2020-3

[8]
Hsa-miR-494-3p attenuates gene HtrA3 transcription to increase inflammatory response in hypoxia/reoxygenation HK2 Cells.

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[9]
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[10]
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引用本文的文献

[1]
Advances in the diagnosis of early biomarkers for acute kidney injury: a literature review.

BMC Nephrol. 2025-3-5

本文引用的文献

[1]
Diagnosis, pathophysiology and preventive strategies for cardiac surgery-associated acute kidney injury: a narrative review.

Eur J Med Res. 2023-1-24

[2]
Serum exosome inflamma-miRs are surrogate biomarkers for asthma phenotype and severity.

Allergy. 2023-1

[3]
Circulating MicroRNAs as Biomarkers of Osteoporosis and Fragility Fractures.

J Clin Endocrinol Metab. 2022-7-14

[4]
3D hESC exosomes enriched with miR-6766-3p ameliorates liver fibrosis by attenuating activated stellate cells through targeting the TGFβRII-SMADS pathway.

J Nanobiotechnology. 2021-12-20

[5]
Mir-184 Contributes to Brain Injury Through Targeting PPAP2B Following Ischemic Stroke in Male Rats.

Front Mol Neurosci. 2021-3-23

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J Med Virol. 2021-7

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Theranostics. 2020

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Annu Int Conf IEEE Eng Med Biol Soc. 2020-7

[9]
Melatonin Enhances the Therapeutic Effect of Plasma Exosomes Against Cerebral Ischemia-Induced Pyroptosis Through the TLR4/NF-κB Pathway.

Front Neurosci. 2020-8-18

[10]
Global epidemiology and outcomes of acute kidney injury.

Nat Rev Nephrol. 2018-10

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