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基于机器学习、单细胞转录组分析和孟德尔随机化揭示VCAN作为糖尿病肾病肾小管和肾小球潜在的共同诊断生物标志物

Revealing VCAN as a Potential Common Diagnostic Biomarker of Renal Tubules and Glomerulus in Diabetic Kidney Disease Based on Machine Learning, Single-Cell Transcriptome Analysis and Mendelian Randomization.

作者信息

Jiang Li, Jian Jie, Sai Xulin, Wu Xiai

机构信息

Diabetes Department of Integrated Chinese and Western Medicine, China National Center for Integrated Traditional Chinese and Western Medicine, China- Japan Friendship Hospital, Beijing, China.

Mental Health Center of Dongcheng District, Beijing, China.

出版信息

Diabetes Metab J. 2025 May;49(3):407-420. doi: 10.4093/dmj.2024.0233. Epub 2025 Jan 24.

Abstract

BACKGRUOUND

Diabetic kidney disease (DKD) is recognized as a significant complication of diabetes mellitus and categorized into glomerular DKDs and tubular DKDs, each governed by distinct pathological mechanisms and biomarkers.

METHODS

Through the identification of common features observed in glomerular and tubular lesions in DKD, numerous differentially expressed gene were identified by the machine learning, single-cell transcriptome and mendelian randomization.

RESULTS

The diagnostic markers versican (VCAN) was identified, offering supplementary options for clinical diagnosis. VCAN significantly highly expressed in glomerular parietal epithelial cell and proximal convoluted tubular cell. It was mainly involved in the up-regulation of immune genes and infiltration of immune cells like mast cell. Mendelian randomization analysis confirmed that serum VCAN protein levels were a risky factor for DKD, while there was no reverse association. It exhibited the good diagnostic potential for estimated glomerular filtration rate and proteinuria in DKD.

CONCLUSION

VCAN showed the prospects into DKD pathology and clinical indicator.

摘要

背景

糖尿病肾病(DKD)被认为是糖尿病的一种重要并发症,分为肾小球性DKD和肾小管性DKD,每种类型由不同的病理机制和生物标志物所调控。

方法

通过识别DKD肾小球和肾小管病变中观察到的共同特征,利用机器学习、单细胞转录组和孟德尔随机化鉴定了众多差异表达基因。

结果

鉴定出诊断标志物多功能蛋白聚糖(VCAN),为临床诊断提供了补充选项。VCAN在肾小球壁层上皮细胞和近端曲管细胞中显著高表达。它主要参与免疫基因的上调和肥大细胞等免疫细胞的浸润。孟德尔随机化分析证实血清VCAN蛋白水平是DKD的一个危险因素,而不存在反向关联。它在DKD的估计肾小球滤过率和蛋白尿方面表现出良好的诊断潜力。

结论

VCAN展现出在DKD病理学和临床指标方面的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a53d/12086553/f28aeb31df1f/dmj-2024-0233f1.jpg

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