Chronic kidney disease (CKD) progression involves tubulointerstitial fibrosis, a process characterized by excessive extracellular matrix accumulation. To identify potential biomarkers for kidney fibrosis, we performed mass spectrometry-based proteomic profiling of human kidney tubular epithelial cells and kidney tissue from a 5/6 nephrectomy rat model. Multidisciplinary analysis across kidney fibrosis models revealed 351 differentially expressed proteins associated with kidney fibrosis, and they were enriched in processes related to the extracellular matrix, kidney aging, and mitochondrial functions. Network analysis of the selected proteins revealed five crucial proteins, of which transgelin emerged as a candidate protein that interacts with known fibrosis-related proteins. Concordantly, the gene expression of transgelin in the kidney tissue from the 5/6 nephrectomy model was elevated. Transgelin expression in kidney tissue gradually increased from intermediate to advanced fibrosis stages in 5/6 Nx rats and mice with unilateral ureteral obstruction. Subsequent validation in kidney tissue and urine samples from patients with CKD confirmed the upregulation of transgelin, particularly under advanced disease stages. Moreover, we investigated whether blocking TAGLN ameliorated kidney fibrosis and reduced reactive oxygen species levels in cellular models. In conclusion, our proteomic approach identified TAGLN as a potential noninvasive biomarker and therapeutic target for CKD-associated kidney fibrosis, suggesting its role in modulating mitochondrial dysfunction and oxidative stress responses.

慢性肾脏病 （CKD） 进展涉及肾小管间质纤维化，这一过程以细胞外基质过度积累为特征。为了确定肾纤维化的潜在生物标志物，我们对 5/6 肾切除术大鼠模型的人肾肾小管上皮细胞和肾组织进行了基于质谱的蛋白质组学分析。肾纤维化模型的多学科分析揭示了 351 种与肾纤维化相关的差异表达蛋白，它们在与细胞外基质、肾脏衰老和线粒体功能相关的过程中富集。所选蛋白质的网络分析揭示了 5 种关键蛋白，其中 transgelin 作为与已知纤维化相关蛋白相互作用的候选蛋白出现。同时，5/6 肾切除术模型肾组织中 transgelin 的基因表达升高。5/6 Nx 大鼠和单侧输尿管梗阻小鼠肾组织中转胶蛋白表达从中度到晚期纤维化阶段逐渐增加。随后在 CKD 患者的肾脏组织和尿液样本中验证证实了 transgelin 的上调，尤其是在疾病晚期。此外，我们研究了阻断 TAGLN 是否改善了细胞模型中的肾纤维化并降低了活性氧水平。总之，我们的蛋白质组学方法将 TAGLN 确定为 CKD 相关肾纤维化的潜在无创生物标志物和治疗靶点，表明它在调节线粒体功能障碍和氧化应激反应中的作用。