Wang Qianhui, Ge Qingmiao, Wang Jingjing, Wu Yonggui, Qi Xiangming
Department of Nephropathy, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Center for Scientific Research of Anhui Medical University, Hefei, Anhui, China.
Endocrine. 2025 Mar;87(3):959-977. doi: 10.1007/s12020-024-04089-4. Epub 2024 Nov 7.
Diabetic kidney disease (DKD) is the primary reason of chronic kidney disease. Our objective was to discover potential autophagy-related biomarkers of tubulointerstitial injury in DKD and assess their clinical value.
We retrieved four datasets (GSE104954, GSE30122, GSE30529, and GSE99340) of renal tubule samples from Gene Expression Omnibus (GEO) and used two algorithms (LASSO and SVM-RFE) to screen for autophagy-related differentially expressed genes (ARDEGs) in DKD. Tripartite motif containing 22 (TRIM22) was identified for subsequent validation. Validation of TRIM22 and autophagic indicators expression in clinical samples and HK-2 cells stimulated by high glucose using immunohistochemistry, immunofluorescence, and western blot.
We identified four ARDEGs (TRIM22, PLK2, HTR2B, and FAS) using a diagnostic gene model. ROC curves further confirmed that TRIM22 had the best diagnostic efficacy for DKD. Both clinical samples and HK-2 cells stimulated by high glucose showed high protein expression of TRIM22. The correlation analysis revealed that TRIM22 correlates with SQSTM1, NGAL, and some clinical and pathological indicators in patients with DKD.
We identified TRIM22 as a potential diagnostic biomarker for DKD, revealing its high diagnostic value in patients with DKD with moderate-to-severe interstitial fibrosis and tubular atrophy (IFTA). TRIM22 is involved in tubulointerstitial injury and autophagy dysregulation in DKD.
糖尿病肾病(DKD)是慢性肾脏病的主要原因。我们的目标是发现DKD中肾小管间质损伤潜在的自噬相关生物标志物,并评估其临床价值。
我们从基因表达综合数据库(GEO)中检索了四个肾小管样本数据集(GSE104954、GSE30122、GSE30529和GSE99340),并使用两种算法(LASSO和SVM-RFE)筛选DKD中自噬相关差异表达基因(ARDEGs)。鉴定出含三联基序蛋白22(TRIM22)用于后续验证。采用免疫组织化学、免疫荧光和蛋白质免疫印迹法验证TRIM22及自噬指标在临床样本和高糖刺激的HK-2细胞中的表达。
我们使用诊断基因模型鉴定出四个ARDEGs(TRIM22、PLK2、HTR2B和FAS)。受试者工作特征(ROC)曲线进一步证实TRIM22对DKD具有最佳诊断效能。临床样本和高糖刺激的HK-2细胞均显示TRIM22蛋白高表达。相关性分析显示,TRIM22与DKD患者的SQSTM1、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)以及一些临床和病理指标相关。
我们鉴定出TRIM22作为DKD的潜在诊断生物标志物,揭示了其在中度至重度间质纤维化和肾小管萎缩(IFTA)的DKD患者中的高诊断价值。TRIM22参与DKD中的肾小管间质损伤和自噬失调。