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Combined Plasma Olink Proteomics and Transcriptomics Identifies CXCL1 and TNFRSF12A as Potential Predictive and Diagnostic Inflammatory Markers for Acute Kidney Injury

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Abstract

Acute kidney injury (AKI) poses a significant global public health challenge. Current methods for detecting AKI rely on monitoring changes in serum creatinine (Scr), blood urea nitrogen (BUN), urinary output and some commonly employed biomarkers. However, these indicators are usually neither specific nor sensitive to AKI, especially in cases of mild kidney injury. AKI is accompanied by severe inflammatory reactions, resulting in the upregulation of numerous inflammation-associated proteins in the plasma. Plasma biomarkers are a noninvasive method for detecting kidney injury, and to date, plasma inflammation-associated cytokines have not been adequately studied in AKI patients. The objective of our research was to identify novel inflammatory biomarkers for AKI. We utilized Olink proteomics to analyze the alterations in plasma inflammation-related proteins in the serum of healthy mice (n = 2) or mice treated with cisplatin (n = 6). Additionally, transcriptome datasets for the lipopolysaccharide (LPS), cisplatin, and ischemia‒reperfusion injury (IRI) groups were obtained from the National Center of Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. We calculated the intersection of differentially expressed proteins (DEPs) and genes (DEGs) from both datasets. In the Olink proteomics analysis, the AKI group had significantly greater levels of 11 DEPs than did the control group. In addition, 56 common upregulated DEGs were obtained from the transcriptome dataset. The expression of CXCL1 and TNFRSF12A overlapped across all the datasets. The transcription and protein expression levels of CXCL1 and TNFRSF12A were detected in vivo. The gene and protein levels of CXCL1 and TNFRSF12A were significantly increased in different AKI mouse models and clinical patients, suggesting that these genes and proteins could be potential specific biomarkers for the identification of AKI.

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The datasets of the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank the Laboratory Animal Center, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital) for providing the experimental mice and their housing conditions.

Funding

This work was supported by the Key Laboratory Construction Plan Project of Shanxi Provincial Health Commission (2023035), Natural Science Foundation of Shanxi Province (202203021222359), Key Medical Research Project of Shanxi Province (2022XM30) and Shanxi Administration of Traditional Chinese Medicine Scientific research project (2023ZYYC2031).

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  1. Xiaoyang Li and Xiangyang Zhou contributed equally.

Authors and Affiliations

  1. Shanxi Provincial Key Laboratory of Kidney Disease, Shanxi Provincial People’s Hospital, Yingze District, 29 Shuangta East Street, Taiyuan, 030000, People’s Republic of China

    Xiaoyang Li, Xiangyang Zhou, Xin Zhao, Huixia Kang, Yuehong Ma, Haijun Ge, Lili Liu, Rongshang Li & Lili Guo

  2. Basic-Medicine of Shanxi Medical University, Yingze District, 56 Xinjian South Road, Taiyuan, 030000, People’s Republic of China

    Xiangyang Zhou & Lili Guo

  3. Second Department of Nephrology, Hospital of Traditional Chinese Medicine of Shanxi Province, Taiyuan, China

    Huixia Kang

  4. The Fifth Clinical Medical College of Shanxi Medical University, Fifth Hospital of Shanxi Medical University, Taiyuan, China

    Yue Zhang

  5. Department of Nephrology, Shanxi Provincial People’s Hospital, Taiyuan, China

    Xinbo Ping & Rongshang Li

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Contributions

Conceived and designed the experiments: LL G. Analyzed the data: XY L and XY Z. Drafted the manuscript: XY L. Performed the experiments: XY L, XY Z, X Z, HX K, HJ G, LL L and YH M. Collection of serum from AKI patients: XB P. Contributed reagents/materials: RS L and LL G. Reviewed and edited the manuscript: LL G. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Lili Guo.

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This study protocol was approved by the Ethics Committee of Shanxi Provincial People's Hospital, and informed consent was obtained from all patients and their families in strict compliance with the Declaration of Helsinki (approved no. 2023–438). This experimental procedure and animal use protocol were approved by the Ethics Committee of Shanxi Provincial People's Hospital (approved no. 2023–439).

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Li, X., Zhou, X., Ping, X. et al. Combined Plasma Olink Proteomics and Transcriptomics Identifies CXCL1 and TNFRSF12A as Potential Predictive and Diagnostic Inflammatory Markers for Acute Kidney Injury. Inflammation (2024). https://doi.org/10.1007/s10753-024-01993-9

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