尿外泌体蛋白 CALM1 的变化可能可作为诊断糖尿病肾病的早期无创性生物标志物。
Changes in urinary exosomal protein CALM1 may serve as an early noninvasive biomarker for diagnosing diabetic kidney disease.
机构信息
Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing 100038, China.
Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing 100038, China; Institute of Regenerative Medicine and Laboratory Technology Innovation, Qingdao University, Qingdao 266071, China.
出版信息
Clin Chim Acta. 2023 Jul 1;547:117466. doi: 10.1016/j.cca.2023.117466. Epub 2023 Jul 3.
BACKGROUND
The risk of the development and progression of diabetic kidney disease (DKD) was increased by abnormal calcium release. However, it is still unknown whether calcium signal pathway-related proteins are changed in urinary exosomes. This study aims to explore the changes in urinary exosomal proteins, which may provide novel biomarkers for diagnosing DKD.
METHODS
Urinary exosomes were isolated from 132 participants by size exclusion chromatography method and 72 participants were tested by LC-MS/MS (Discovery phase). Correlation and multivariate logistics analysis were applied to evaluate selected urinary proteins. Western blot and ELISA were used to validate the selected protein (Validation phase: n = 60). The diagnostic performance of the selected biomarker was evaluated by receiver operating characteristic curve analyses between the discovery and validation phases.
RESULTS
Sixteen calcium signal pathway-related proteins were identified, however, only Calmodulin-1(CALM1) was continuously increased. Different expression of CALM1 was found in patients with different level of estimated glomerular filtration rate (eGFR) in two cohorts. The level of CALM1 was correlated with eGFR and serum creatinine levels in two cohorts. Multivariate analysis revealed that serum albumin (ALB) levels and CALM1 were independent risk factors for DKD. A diagnostic model based on CALM1 and serum ALB levels that could significantly distinguish DKD was established and validated.
CONCLUSIONS
Significant changes in calcium signal pathway-related urinary exosomal proteins were observed. The CALM1 may serve as an early noninvasive biomarker for diagnosing DKD.
背景
钙释放异常会增加糖尿病肾病（DKD）的发生和进展风险。然而，尿外泌体中钙信号通路相关蛋白是否发生改变仍不清楚。本研究旨在探讨尿外泌体蛋白的变化，以期为 DKD 的诊断提供新的生物标志物。
方法
采用排阻色谱法从 132 例参与者的尿液中分离尿外泌体，并用 LC-MS/MS 对其中 72 例进行检测（发现阶段）。应用相关性和多元逻辑回归分析评估选定的尿蛋白。用 Western blot 和 ELISA 验证选定的蛋白（验证阶段：n=60）。在发现和验证阶段，通过受试者工作特征曲线分析评估所选生物标志物的诊断性能。
结果
共鉴定出 16 种钙信号通路相关蛋白，其中仅钙调蛋白-1（CALM1）持续升高。在两个队列中，不同 eGFR 水平的患者尿外泌体中 CALM1 表达水平不同。CALM1 水平与两个队列的 eGFR 和血清肌酐水平相关。多因素分析显示血清白蛋白（ALB）水平和 CALM1 是 DKD 的独立危险因素。建立并验证了基于 CALM1 和血清 ALB 水平的 DKD 诊断模型。
结论
钙信号通路相关尿外泌体蛋白发生显著变化。CALM1 可能作为一种早期无创的 DKD 诊断生物标志物。
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