Xia Xiaoping, Liu Renyang, Jiang Xiaohui
Department of Intensive Care Unit, Taizhou Integrated Traditional Chinese and Western Medicine Hospital, Wenling, Zhejiang, China.
Emergency and Critical Care Center, Intensive Care Unit, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
Ren Fail. 2025 Dec;47(1):2502608. doi: 10.1080/0886022X.2025.2502608. Epub 2025 May 14.
Acute kidney injury (AKI) is a life-threatening condition with limited early biomarkers. Mitochondrial dysfunction is central to AKI pathophysiology, yet its potential for predicting AKI remains underexplored.
Gene expression data from three publicly available AKI datasets (GSE30718, GSE61739, and GSE139061) were analyzed to identify differentially expressed genes (DEGs). A set of 11 mitochondrial-related genes was selected and used to construct a mitochondrial risk score (MRS) model Lasso and elastic net regression. The model was validated across multiple datasets. Immune infiltration was assessed using the xCell algorithm to explore the relationship between MRS and immune cell dynamics in AKI. Stable HK-2 cells were constructed of XRCC3 knockdown and overexpression to investigate the effects of XRCC3 on cell activities. Additionally, the impact of XRCC3 on mitochondrial structure and function was examined and .
Eleven mitochondrial-related genes were consistently dysregulated across all datasets. PCA demonstrated a clear separation between AKI and normal samples. Functional enrichment analysis revealed that upregulated genes were linked to extracellular matrix remodeling and stress responses, while downregulated genes were associated with mitochondrial dysfunction. The MRS model showed strong predictive performance. We found that XRCC3 significantly promoted the activities of HK-2 cells and improved the integrity of mitochondrial structure and function and .
The mitochondrial gene-based MRS model is a robust tool for predicting AKI. Our findings underscore the critical role of mitochondrial dysfunction and immune modulation in AKI, offering potential avenues for targeted therapeutic strategies.
急性肾损伤（AKI）是一种危及生命的疾病，早期生物标志物有限。线粒体功能障碍是AKI病理生理学的核心，但对其预测AKI的潜力仍未充分探索。
分析来自三个公开可用的AKI数据集（GSE30718、GSE61739和GSE139061）的基因表达数据，以鉴定差异表达基因（DEG）。选择一组11个线粒体相关基因，用于构建线粒体风险评分（MRS）模型。通过套索回归和弹性网络回归进行分析。该模型在多个数据集上进行了验证。使用xCell算法评估免疫浸润，以探讨MRS与AKI中免疫细胞动态之间的关系。构建了XRCC3基因敲低和过表达的稳定HK-2细胞系，以研究XRCC3对细胞活性的影响。此外，还检测了XRCC3对线粒体结构和功能的影响。
所有数据集中，11个线粒体相关基因均持续失调。主成分分析（PCA）显示AKI样本与正常样本之间有明显区分。功能富集分析表明，上调基因与细胞外基质重塑和应激反应有关，而下调基因与线粒体功能障碍有关。MRS模型显示出强大的预测性能。我们发现XRCC3显著促进HK-2细胞的活性，并改善线粒体结构和功能的完整性。
基于线粒体基因的MRS模型是预测AKI的有力工具。我们的研究结果强调了线粒体功能障碍和免疫调节在AKI中的关键作用，为靶向治疗策略提供了潜在途径。
