Comprehensive Network-Based Analyses Reveal Novel Renal Function-Related Targets in Acute Kidney Injury

基于网络的综合分析揭示急性肾损伤中新的肾功能相关靶点

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作者:Yang Zhang, Jieru Cai, Wei Lu, Sujuan Xu, Mengdi Qu, Shuan Zhao, Xiaoqiang Ding

Background

Acute kidney injury (AKI) is a common clinical syndrome with limited

Conclusion

The analysis suggests that WGCNA is a proper method to connect clinical traits with genome data to find novel targets in AKI. The kidney tissue with worse renal function tended to develop a "high immune but low metabolic activity" expression pattern. Also, ACSM2A, GLYAT, CORO1A, DPEP1, ALDH7A1, and EPHX2 are potential targets of molecular diagnosis and treatment in AKI.

Methods

First, by employing WGCNA in transcriptional data on 30 patients with well/poor functioning kidney graft, we identified two co-expression modules that were significantly related to serum creatinine (SCr). Second, based on the modules, potential small molecular compound candidates for developing targeted therapeutics were obtained by connectivity map analysis. Furthermore, multiple validations of expression in space/time were carried out with two classical AKI models in vivo and other five databases of over 152 samples.

Results

Two of the 14 modules were found to be closely correlated with SCr. Function enrichment analysis illustrated that one module was enriched in the immune system, while the other was in the metabolic process. Six key renal function-related genes (RFRGs) were finally obtained. Such genes performed well in cisplatin-induced or cecal ligation and puncture-induced AKI mouse models.

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