FGA Serves as a Potential Diagnostic Marker and Therapeutic Target for Elderly Acute Kidney Injury.

Journal: Journal of proteome research
Published Date:

Abstract

To identify potential biomarkers and explore the underlying mechanisms of elderly acute kidney injury (e-AKI), we performed integrative plasma proteomics analysis on samples from 20 e-AKI patients and 20 age-matched non-AKI controls. Differential expression gene analysis, GSEA, WGCNA, random forest, and LASSO models were employed to identify hub genes, coupled with immune cell infiltration and clinicopathological correlation analyses. A renal ischemia-reperfusion injury mouse model validated key genes at protein and mRNA levels, while in vitro experiments explored the pathway involvement. We identified 229 e-AKI-associated genes enriched in immune, inflammatory, and coagulation pathways. Machine learning combined with the Nephroseq database yielded three hub genes; in vivo and in vitro experiments confirmed fibrinogen alpha chain (FGA) as the most relevant gene, which may regulate e-AKI progression via the cAMP/PKA/CREB pathway. Collectively, FGA holds promise as a diagnostic biomarker and therapeutic target for e-AKI, laying the theoretical foundation for its mechanistic research.

Authors

  • Hong Yu
    University of Massachusetts Medical School, Worcester, MA.
  • Jiacen Dai
    Department of Urology, School of Medicine, Wuhan Third Hospital, Wuhan University of Science and Technology, Wuhan 430060, China.
  • Shuping Deng
    Department of Intensive Care Unit, Wuhan Third Hospital and Tongren Hospital of Wuhan University, Wuhan 430060, China.
  • Lingwen Xu
    Department of Electrical and Computer Engineering, University of Washington, Seattle, Washington 98195, United States.
  • Qihui Kuang
    Department of Urology, Wuhan Third Hospital and Tongren Hospital of Wuhan University, Wuhan 430060, China.
  • Xiao Wei
    Guangxi Medical University, Nanning, Guangxi, China.
  • Yuan Yuan
    Department of Geriatrics, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China.
  • Fang Dong
    Key Laboratory of Coastal Biology and Bioresource Utilization, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China. [email protected].
  • Xiong Wang
  • Pengcheng Luo
    Department of Urology, Wuhan Third Hospital and Tongren Hospital of Wuhan University, Wuhan 430060, China.

Keywords

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