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小鼠轻度至重度肾缺血/再灌注诱导的肾损伤中的转录进展模式。

Transcriptional progressive patterns from mild to severe renal ischemia/reperfusion-induced kidney injury in mice.

作者信息

Lai Dong, Wang Lei, Li Jia-Rui, Chen Chen, Zhao Wen-Lei, Yuan Qing, Ma Xin, Zhang Xu

机构信息

Department of Urology, The Third Medical Center, Chinese PLA General Hospital, Beijing, China.

Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.

出版信息

Front Genet. 2022 Jul 22;13:874189. doi: 10.3389/fgene.2022.874189. eCollection 2022.

Abstract

The renal ischemia/reperfusion (I/R)-induced acute kidney injury incidence after nephron-sparing surgery for localized renal tumors is 20%, but the biological determinant process of postoperative acute kidney injury remains unclear. Using Gene Expression Omnibus database (GSE192883) and several bioinformatics analyses (discrete time points analysis, gene set enrichment analysis, dynamic network biomarker analysis, etc), combined with the establishment of the I/R model for verification, we identified three progressive patterns involving five core pathways confirmed using gene set enrichment analysis and six key genes (, , , , , and ) verified using quantitative polymerase chain reaction The dynamic network biomarker (DNB) subnetwork composite index value is the highest in the 22-min ischemia group, suggesting the transcriptome expression level fluctuated sharply in this group, which means 22-min ischemia is an critical warning point. This study illustrates the core molecular progressive patterns from mild to severe I/R kidney injury, laying the foundation for precautionary biomarkers and molecular intervention targets for exploration. In addition, the safe renal artery blocking time of nephron-sparing surgery that we currently accept may not be safe anymore.

摘要

局限性肾肿瘤保留肾单位手术后肾缺血/再灌注(I/R)诱导的急性肾损伤发生率为20%,但术后急性肾损伤的生物学决定过程仍不清楚。利用基因表达综合数据库(GSE192883)和几种生物信息学分析(离散时间点分析、基因集富集分析、动态网络生物标志物分析等),并结合建立I/R模型进行验证,我们确定了三种进展模式,涉及通过基因集富集分析确认的五条核心通路和通过定量聚合酶链反应验证的六个关键基因(、、、、、和)。动态网络生物标志物(DNB)子网复合指数值在22分钟缺血组中最高,表明该组转录组表达水平波动剧烈,这意味着22分钟缺血是一个关键警告点。本研究阐明了从轻度到重度I/R肾损伤的核心分子进展模式,为探索预防性生物标志物和分子干预靶点奠定了基础。此外,我们目前所接受的保留肾单位手术的安全肾动脉阻断时间可能不再安全。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/650e/9355309/136efd598748/fgene-13-874189-g001.jpg

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