机构：[1]Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200437, China.[2]Department of Nephrology, Sichuan Academy of Sciences & Sichuan Provincial People's Hospital, Sichuan Clinical Research Center for Kidney Disease, University of Electronic Science and Technology, Chengdu 610072, China.四川省人民医院[3]Department of Nephrology, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, China.[4]Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Minister of Education, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
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.
基金：
This work was supported by Shanghai Science and Technology Innovation Action Plan
(19DZ2205600, 21002411500), the Shanghai Municipal Key Clinical Specialty (shslczdzk02501), Shanghai
Key Laboratory of Kidney and Blood Purification, Shanghai Science and Technology Commission
(20DZ2271600), China National Key R&D Program during the 13th Five-year Plan Period (Grant
No. 2020YFE0202200-1), China National Key R&D Program during the 14th Five-year Plan Period
(Grant No. 2022YFC3400202), the National Natural Science Foundation of China (Grant No. 31971352
and 32171432), and the Science and Technology Commission of Shanghai Municipality (Grant No.
18JC1411103, 19JC1411002, 19JC1411003, 19JC1411000 and 20511104702).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类|2 区化学
小类|3 区生化与分子生物学3 区化学：综合
最新[2025]版：
大类|3 区化学
小类|3 区生化与分子生物学3 区化学：综合
第一作者：
第一作者机构：[1]Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200437, China.
通讯作者：
推荐引用方式(GB/T 7714)：
Li Qing,Zhang Jiong,Fang Yi,et al.Phosphoproteome Profiling of uEVs Reveals p-AQP2 and p-GSK3β as Potential Markers for Diabetic Nephropathy[J].Molecules (Basel, Switzerland).2023,28(14):doi:10.3390/molecules28145605.
APA：
Li Qing,Zhang Jiong,Fang Yi,Dai Yan,Jia Ping...&Zhou Feng.(2023).Phosphoproteome Profiling of uEVs Reveals p-AQP2 and p-GSK3β as Potential Markers for Diabetic Nephropathy.Molecules (Basel, Switzerland),28,(14)
MLA：
Li Qing,et al."Phosphoproteome Profiling of uEVs Reveals p-AQP2 and p-GSK3β as Potential Markers for Diabetic Nephropathy".Molecules (Basel, Switzerland) 28..14(2023)
