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- Title
Phosphoproteome Profiling of uEVs Reveals p-AQP2 and p-GSK3β as Potential Markers for Diabetic Nephropathy.
- Authors
Li, Qing; Zhang, Jiong; Fang, Yi; Dai, Yan; Jia, Ping; Shen, Ziyan; Xu, Sujuan; Ding, Xiaoqiang; Zhou, Feng
- Abstract
Diabetic nephropathy (DN) contributes to increased morbidity and mortality among patients with diabetes and presents a considerable global health challenge. However, reliable biomarkers of DN have not yet been established. Phosphorylated proteins are crucial for disease progression. However, their diagnostic potential remains unexplored. In this study, we used ultra-high-sensitivity quantitative phosphoproteomics to identify phosphoproteins in urinary extracellular vesicles (uEVs) as potential biomarkers of DN. We detected 233 phosphopeptides within the uEVs, with 47 phosphoproteins exhibiting significant alterations in patients with DN compared to those in patients with diabetes. From these phosphoproteins, we selected phosphorylated aquaporin-2 (p-AQP2[S256]) and phosphorylated glycogen synthase kinase-3β (p-GSK3β[Y216]) for validation, as they were significantly overrepresented in pathway analyses and previously implicated in DN pathogenesis. Both phosphoproteins were successfully confirmed through Phos-tag western blotting in uEVs and immunohistochemistry staining in kidney sections, suggesting that phosphoprotein alterations in uEVs reflect corresponding changes within the kidney and their potential as candidate biomarkers for DN. Our research proposes the utilization of phosphoproteins in uEVs as a liquid biopsy, presenting a highly feasible diagnostic tool for kidney disease.
- Subjects
DIABETIC nephropathies; PHOSPHOPROTEINS; EXTRACELLULAR vesicles; KIDNEY diseases; WESTERN immunoblotting; AQUAPORINS; GLYCOGEN synthase kinase-3; CIRCULATING tumor DNA
- Publication
Molecules, 2023, Vol 28, Issue 14, p5605
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules28145605